The role of mitochondria in rheumatic diseases

In the paper

“The oxidation of mitochondrial epitopes during apoptosis might lead to formation of neoantigens that are recognized by anti-mitochondrial antibodies228.”

What the sources say

• Disputed

  The Discussion (page not provided) says that oxidation of PDC-E2 during apoptosis causes loss of the epitope recognized by primary biliary cirrhosis patient autoantibodies. It proposes that the reduced, unmodified form—not the oxidized form—activates PDC-E2-specific B cells. Although the Introduction raises the general possibility of apoptotic neoantigens, the paper's finding runs contrary to the claimed antibody recognition of oxidized mitochondrial epitopes. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites [228] Odin, J. A., Huebert, R. C., Casciola-Rosen, L., LaRusso, N. F. & Rosen, A. Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. J. Clin. Invest. 108, 223–232 (2001). sourceExperimental — accuracy not yet measured

In the paper

“In some European populations, individuals harbouring the mitochondrial haplogroups J and T have a decreased risk of developing osteoarthritis and psoriatic arthritis compared with the rest of the population36,37”

What the sources say

• Partly supported

  The Discussion reports a protective association between haplogroup J and osteoarthritis in Spanish cohorts; Results §3.2 reports a lower probability of osteoarthritis for haplogroup T in the UK cohort. The paper does not report a decreased risk of psoriatic arthritis, so that part of the claim is unsupported. (LLM, conf=0.89)

  cites [36] Soto-Hermida, A. et al. mtDNA haplogroups and osteoarthritis in different geographic populations. Mitochondrion 15, 18–23 (2014). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [37] Coto-Segura, P. et al. Common European mitochondrial haplogroups in the risk for psoriasis and psoriatic arthritis. Genet. Test. Mol. Biomark. 16, 621–623 (2012). source

In the paper

“Some of the non-synonymous changes within MT-ND1 generated predicted epitopes for RA-predisposing MHC class II alleles (HLA-DRβ1*0101 and HLA-DRβ1*0401), suggesting a role for these mutations in RA pathogenesis44”

What the sources say

• Supported

  The Results section (‘Epitope prediction and somatic mutations’) reports that five investigated epitopes were changed in RA samples and that all the changed RA epitopes exceeded the predicted binding cutoff. The Discussion (‘Altered mitochondrial proteins as non-self’) identifies HLA-DRβ1*0101 and HLA-DRβ1*0401 as RA-associated alleles and proposes that recognition of mutated mitochondrial peptides may help sustain RA synovial inflammation. (LLM, conf=0.93)

  cites [44] Da Sylva, T. R., Connor, A., Mburu, Y., Keystone, E. & Wu, G. E. Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes. Arthritis Res. Ther. 7, R844–R851 (2005). source

In the paper

“these organelles express biomolecules that resemble those expressed by prokaryotes, such as cardiolipin, double-stranded-hypomethylated DNA and N-formylated peptides12,13”

What the sources say

• ?Not checked — no full text of the sourcecites [12] Krysko, D. V. et al. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol. 32, 157–164 (2011). source
• Partly supported

  The paper’s Abstract says mitochondrial DNA resembles bacterial DNA in having nonmethylated CpG motifs and identifies mitochondrial formyl peptides as bacterial-like molecular signatures. It does not identify cardiolipin among those signatures or specify that the DNA is double-stranded; those details are not supported by our copy. (LLM, conf=0.88)

  cites [13] Zhang, Q. et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464, 104–107 (2010). sourceExperimental — accuracy not yet measured

In the paper

“one study reported an increase in the frequency of mtDNA somatic mutations in synoviocytes from patients with RA compared with synoviocytes from patients with OA44”

What the sources say

• Supported

  The Results section (‘Mutational burden in OA and RA’) reports significantly more mtDNA changes per base pair in RA patients than in OA controls, in both synovial tissue and synovial fibroblasts. The Abstract likewise reports about twice as many mutations in RA synoviocyte mtDNA. (LLM, conf=0.94)

  cites [44] Da Sylva, T. R., Connor, A., Mburu, Y., Keystone, E. & Wu, G. E. Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes. Arthritis Res. Ther. 7, R844–R851 (2005). source

In the paper

“MtDNA haplogroups with pathogenic SNPs can contribute to metabolic, late-onset neurodegenerative diseases and autoimmune diseases through various mechanisms32,33”

What the sources say

• Partly supported

  The 'Mitochondrial haplotypes as modifiers' section says pathogenic mtDNA mutations can cause diabetes and describes a haplogroup modifying the effects of an optic-neuropathy mutation. But 'Susceptibility to complex disorders' calls links between haplogroups and metabolic or neurodegenerative disorders highly controversial and concludes that the evidence is too weak to establish a contribution. The paper mentions an autoimmune response to mitochondrial dysfunction, not autoimmune disease caused by haplogroups carrying pathogenic SNPs. (LLM, conf=0.88)

  cites [32] Schon, E. A., DiMauro, S. & Hirano, M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat. Rev. Genet. 13, 878–890 (2012). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and the sections on endocrine and nervous-system diseases (page numbers unavailable) link mtDNA variants and haplogroups to metabolic disorders and neurodegenerative diseases. The paper does not establish a link to autoimmune diseases, and its Conclusions say the specific disease mechanisms require further investigation. (LLM, conf=0.85)

  cites [33] Sun, D., Wei, Y., Zheng, H. X., Jin, L. & Wang, J. Contribution of mitochondrial DNA variation to chronic disease in East Asian populations. Front. Mol. Biosci. 6, 128 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Individuals with D-loop polymorphisms (namely, polycytidine (polyC) alterations) have lower mtDNA copy numbers than individuals with intact D-loops38,39”

What the sources say

• Partly supported

  Results and Discussion (§2.2–2.3; page unavailable) report that declining leukocyte mtDNA copy number with increasing SLE disease activity was more pronounced in patients with D310 heteroplasmy. The paper does not establish the broader claim that individuals with polycytidine alterations have lower copy numbers than individuals with intact D-loops; its reported comparison concerns disease activity within the studied SLE patients. (LLM, conf=0.86)

  cites [38] Lee, H. T. et al. Leukocyte mitochondrial DNA alteration in systemic lupus erythematosus and its relevance to the susceptibility to lupus nephritis. Int. J. Mol. Sci. 13, 8853–8868 (2012). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [39] Liou, C. W. et al. Association between a common mitochondrial DNA D-loop polycytosine variant and alteration of mitochondrial copy number in human peripheral blood cells. J. Med. Genet. 47, 723–728 (2010). source

In the paper

“Some D-loop polyC variants are associated with susceptibility to SLE and disease severity, including alterations at nt16189 (a T > C polymorphism) and in the D310 region38,40”

What the sources say

• Supported

  Results §§2.1–2.2 report more frequent D310 heteroplasmy in SLE patients than controls and an increasing frequency with higher disease-activity scores. Section 2.4 also links more D310 variants to lupus nephritis. This confirms the D310 portion of the sentence; the nt16189 example is not attributed specifically to this paper in the multi-cited sentence. (LLM, conf=0.90)

  cites [38] Lee, H. T. et al. Leukocyte mitochondrial DNA alteration in systemic lupus erythematosus and its relevance to the susceptibility to lupus nephritis. Int. J. Mol. Sci. 13, 8853–8868 (2012). source
• ?Not checked — no full text of the sourcecites [40] Jonsen, A. et al. Mitochondrial DNA polymorphisms are associated with susceptibility and phenotype of systemic lupus erythematosus. Lupus 18, 309–312 (2009). source

In the paper

“These events can lead to the generation of neoantigens that could be recognized as exogenous threats by the adaptive immune system68”

What the sources say

• Supported

  The Environmental sources of oxidative stress section says oxidative modification can generate autoantigens. The Oxidative autoantigenesis section describes immune recognition of those altered self-antigens, including antibody responses to oxidized DNA and HNE-modified proteins. This supports the claim’s hedged description of oxidative events creating antigens that the adaptive immune system may treat as threats; the paper does not use the word “exogenous.” (LLM, conf=0.88)

  cites [68] Perl, A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat. Rev. Rheumatol. 9, 674–686 (2013). source

In the paper

“Investigations of C1q or C3 deficiency in a chronic graft-versus-host-disease model of SLE indicate that C1q, but not C3, could modulate mitochondrial metabolism in CD8+ T cells to limit self-reactive responses81”

What the sources say

• Supported

  The Abstract states that, in a mouse model of SLE, C1q but not C3 restrains responses to self-antigens by modulating CD8+ T-cell mitochondrial metabolism. The passage describing the methods identifies the model as chronic graft-versus-host disease; our copy provides no page numbers. (LLM, conf=0.94)

  cites [81] Ling, G. S. et al. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360, 558–563 (2018). source

In the paper

“signalling pathways involving the T cell receptor (TCR), CD28 and the PI3K–Akt–mTOR axis upregulate the expression of glucose transporter 1 (GLUT1), increasing the rate of aerobic glycolysis71,72”

What the sources say

• Partly supported

  The “Glucose and proliferating T cells” section says TCR stimulation moves Glut1 to the cell surface, while CD28 signals increase its expression and surface localization. The “Conventional view of T-cell metabolism” section links CD28–PI3K–AKT and mTOR signaling to increased glycolysis. It does not say that TCR signaling increases Glut1 expression, or specifically that mTOR increases Glut1 expression; page numbers were not supplied. (LLM, conf=0.85)

  cites [71] van der Windt, G. J. & Pearce, E. L. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol. Rev. 249, 27–42 (2012). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [72] Frauwirth, K. A. et al. The CD28 signaling pathway regulates glucose metabolism. Immunity 16, 769–777 (2002). source

In the paper

“Biomolecules provided by the diet are also able to modulate mitochondrial activity in various metabolic pathways, such as those involved in energy supply, mitochondrial dynamics and mtROS production84”

What the sources say

• Partly supported

  The Abstract and Introduction link diet-derived metabolites to metabolic pathways and identify mitochondria as sources of ATP and reactive oxygen intermediates. They do not establish that dietary biomolecules modulate mitochondrial dynamics or mitochondrial reactive oxygen species production; searches for those links found no supporting passage. (LLM, conf=0.84)

  cites [84] Oaks, Z. & Perl, A. Metabolic control of the epigenome in systemic lupus erythematosus. Autoimmunity 47, 256–264 (2014). sourceExperimental — accuracy not yet measured

In the paper

“short-lived effector cells, expanded in the absence of C1q, contribute to self-reactive responses and tissue inflammation”

What the sources say

• Supported

  In the paper’s text (section labeled Abstract; page unavailable), C1q-deficient mice in a lupus-like disease model had a relative expansion of short-lived effector CD8+ T cells. The authors report that CD8+ T cells perpetuated the autoimmune response and propose that effector CD8+ T cells propagate autoimmunity and tissue damage. The claim summarizes those findings rather than a test isolating the short-lived subset. (LLM, conf=0.88)

  cites [81] Ling, G. S. et al. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360, 558–563 (2018). source

In the paper

“These cells might contribute to SLE pathogenesis and end organ damage via supporting extrafollicular humoral responses75”

What the sources say

• Supported

  The paper describes Th10 cells as B-cell helpers and says targeting their pathway might blunt extrafollicular humoral responses in SLE (passage 1, labeled Abstract). It also says Th10 cells might contribute to SLE pathogenesis and end-organ damage (passage 4, labeled Abstract). The citing sentence preserves that uncertainty. (LLM, conf=0.91)

  cites [75] Caielli, S. et al. A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate. Nat. Med. 25, 75–81 (2019). source

In the paper

“mitochondrial dysfunction in rodent models of arthritis could be reduced via treatment with statins or antioxidants (for example, Coenzyme Q10 or omega-3)87,88”

What the sources say

• ?Not checked — no full text of the sourcecites [87] Farnaghi, S. et al. Protective effects of mitochondria-targeted antioxidants and statins on cholesterol-induced osteoarthritis. FASEB J. 31, 356–367 (2017). source
• Partly supported

  The Summary (p. 1) and Discussion (p. 7) report that coenzyme Q10 and omega-3 fatty acids improved skeletal-muscle mitochondrial function in arthritic rats. The cited paper does not support the sentence’s statin-treatment claim. (LLM, conf=0.88)

  cites [88] Kucharská, J. et al. Treatment with coenzyme Q10, ω-3-polyunsaturated fatty acids and their combination improved bioenergetics and levels of coenzyme Q9 and Q10 in skeletal muscle mitochondria in experimental model of arthritis. Physiol. Res. 70, 723–733 (2021). sourceExperimental — accuracy not yet measured

In the paper

“In mice, the expression of C1qBP is higher in effector CD8+ T cells than in naive cells”

What the sources say

• Partly supported

  The passage discussing Fig. S11B–C reports increased p32/gC1qR expression on activated mouse CD8+ T cells. It does not explicitly compare effector CD8+ T cells with naïve cells, so the claim is more specific than the reported finding. (LLM, conf=0.78)

  cites [81] Ling, G. S. et al. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360, 558–563 (2018). sourceExperimental — accuracy not yet measured

In the paper

“In the blood of patients with SLE, concomitant oxidation of mtDNA and signalling through the Notch pathway induce the expansion of a unique population of CD4+ T cells (CXCR5−CXCR3+PD1hiCD4+ T cells, known as T helper 10 (TH10) cells)75,76”

What the sources say

• Partly supported

  The paper reports that CXCR5− CXCR3+ PD1hi CD4+ T cells are expanded in SLE blood and that similar cells can be generated in vitro using plasmacytoid dendritic cells activated by oxidized mtDNA (Abstract; passage [2]). It does not establish that oxidized mtDNA and Notch signalling act together to induce their expansion in patients, and our copy does not identify the cells as TH10 (searched: Notch, TH10). (LLM, conf=0.88)

  cites [75] Caielli, S. et al. A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate. Nat. Med. 25, 75–81 (2019). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [76] Caielli, S., Banchereau, J. & Pascual, V. Dissecting the mechanisms responsible for the generation of regulatory versus pathogenic human CD4+ T cells by TLR9-activated plasmacytoid dendritic cells. J. Immunol. 204, 230.233–230.233 (2020). source

In the paper

“The C1q binding protein (C1qBP, also known as p32 or gC1qR) is considered a modulator of mitochondrial activity through its ability to regulate protein translation within the organelle82”

What the sources say

• Supported

  The Results section, “Reduced mitochondrial translation rate” (page unavailable), reports that mitochondrial protein synthesis was markedly reduced in p32-deficient cells and partially restored when p32 was re-expressed. The Discussion (page unavailable) links this translation defect to impaired respiratory-chain activity, supporting the description of C1qBP/p32 as a modulator of mitochondrial activity through mitochondrial protein synthesis. (LLM, conf=0.93)

  cites [82] Yagi, M. et al. p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability. Nucleic Acids Res. 40, 9717–9737 (2012). source

In the paper

“confocal microscopy analyses indicate that C1q and C1qBP co-localized in mitochondria”

What the sources say

• Supported

  The paper’s main text (indexed under “Abstract”; page unavailable) states that C1q co-localised with the mitochondrial receptor p32/gC1qR, also called C1qBP, and points to Fig. 4H. This supports the claimed mitochondrial co-localization, though the passage does not name confocal microscopy explicitly. (LLM, conf=0.90)

  cites [81] Ling, G. S. et al. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360, 558–563 (2018). source
• Partly supported

  The passage labeled Abstract (page unavailable) says that C1q bound to its receptor p32 and translocated to mitochondria, supporting an association there. It does not identify p32 as C1qBP or report confocal microscopy showing co-localization, so the specific imaging claim is not established by this copy. (LLM, conf=0.82)

  cites [83] Weyand, C. M. & Goronzy, J. J. A mitochondrial checkpoint in autoimmune disease. Cell Metab. 28, 185–186 (2018). sourceExperimental — accuracy not yet measured

In the paper

“the existence of redundant mechanisms in clearing apoptotic debris, including those mediated by C3 and complement activation independent of C1q79,80, suggest that C1q has an alternative function in maintaining self-tolerance in SLE”

What the sources say

• ?Not checked — no full text of the sourcecites [79] Martin, M. & Blom, A. M. Complement in removal of the dead — balancing inflammation. Immunol. Rev. 274, 218–232 (2016). source
• Partly supported

  Section 2.4 (page unavailable) describes an immunoregulatory role for C1q beyond debris clearance: it promotes anti-inflammatory responses and limits responses to self-antigens, consistent with maintaining self-tolerance. But the paper does not establish the claimed redundancy of apoptotic-debris clearance mechanisms; it instead describes a predominant role for C1q over C1 activation and C3b deposition in apoptotic-cell clearance and immunosuppression. (LLM, conf=0.84)

  cites [80] Thielens, N. M., Tedesco, F., Bohlson, S. S., Gaboriaud, C. & Tenner, A. J. C1q: a fresh look upon an old molecule. Mol. Immunol. 89, 73–83 (2017). sourceExperimental — accuracy not yet measured

In the paper

“numerous metabolic pathways are downregulated in CD8+ T cells in patients with SLE”

What the sources say

• Partly supported

  The Results section, “Downregulation of OXPHOS genes in patients with high expression of ISGs” (page unavailable), reports downregulation of pathways involved in the TCA cycle, electron transport chain, and ATP synthesis, more pronounced in CD8+ T cells. The comparison is specifically between SLE patients with high and lower interferon signatures; the claim omits that restriction and reads as applying to patients with SLE generally. (LLM, conf=0.85)

  cites [74] Buang, N. et al. Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus. Nat. Commun. 12, 1980 (2021). sourceExperimental — accuracy not yet measured

In the paper

“a genetic variant of F0F1–ATP synthase is associated with the development of SLE35”

What the sources say

• Supported

  The Results section reports that the nt9055 variant remained significantly associated with SLE after correction for multiple testing. The Discussion identifies nt9055 as a variant in the ATP6, or F0F1-ATPase, gene. This supports an association with SLE, though it does not establish that the variant causes the disease. (LLM, conf=0.94)

  cites [35] Vyshkina, T. et al. Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus. Clin. Immunol. 129, 31–35 (2008). source

In the paper

“In various cell types, metabolic aberrations induced by mitochondrial abnormalities are linked to self-reactive and inflammatory phenotypes in autoimmune conditions, including SLE and RA68,69”

What the sources say

• Partly supported

  The sections on diminished antioxidant defences and oxidative autoantigenesis link mitochondrial dysfunction and oxidative stress in SLE to autoreactivity and inflammation. The section on increased mitochondrial ROI production also associates a mitochondrial-protein variant with predisposition to RA, but it does not establish the claimed link to self-reactive or inflammatory phenotypes in RA. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  cites [68] Perl, A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat. Rev. Rheumatol. 9, 674–686 (2013). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [69] Lee, H. T. et al. The pathogenesis of systemic lupus erythematosus — from the viewpoint of oxidative stress and mitochondrial dysfunction. Mitochondrion 30, 1–7 (2016). source

In the paper

“these cells express higher levels of interferon-stimulated genes compared with those of healthy individuals”

What the sources say

• Supported

  The Results section ('Downregulation of OXPHOS genes in patients with high expression of ISGs'; page not available) compares SLE T cells with healthy controls and reports enriched IFN-signaling pathways in SLE CD8+ T cells. It also reports increased ISG expression in the CD8+ T cells of the SLE subgroup with a stronger IFN signature. (LLM, conf=0.88)

  cites [74] Buang, N. et al. Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus. Nat. Commun. 12, 1980 (2021). source

In the paper

“Extrusion of mtDNA can also occur through NET formation57.”

What the sources say

• Supported

  The Results section (‘RNP ICs induce oxidized mtDNA release’) reports increased mtDNA in released NETs following RNP IC activation, alongside a decrease in intracellular mtDNA. This directly supports the claim that mtDNA extrusion can occur through NET formation. (LLM, conf=0.94)

  cites [57] Lood, C. et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med. 22, 146–153 (2016). source

In the paper

“In homeostasis, RAB4A promotes lysosomal degradation of DRP1, subsequently inhibiting mitochondrial fission and mitophagy”

What the sources say

• Partly supported

  The Results section ('HRES-1/Rab4 promotes the lysosomal degradation of Drp1'; page not provided) reports that HRES-1/Rab4 overexpression depleted Drp1, with evidence implicating lysosomal degradation. The Results and Discussion link HRES-1/Rab4 to inhibited mitophagy, while the Introduction identifies Drp1 as initiating mitochondrial fission. The paper establishes these effects chiefly in overexpression experiments, not specifically as a process occurring 'in homeostasis.' (LLM, conf=0.84)

  cites [116] Caza, T. N. et al. HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Ann. Rheum. Dis. 73, 1888–1897 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Mechanistically, in neutrophils activated by immune complexes containing U1 small nuclear ribonucleoproteins (SnRNPs), mitochondria generate excessive amounts of ROS, which supports the formation and extrusion of NETs”

What the sources say

• Partly supported

  The Results section on RNP immune complex–mediated NETosis reports increased mitochondrial ROS after neutrophil activation and shows that inhibiting mitochondrial activity reduces NET formation. The Online methods describe the complexes as containing SmRNP antigen and anti-RNP antibodies, but our copy does not identify the antigen specifically as U1 snRNP. No page numbers are available in our copy. (LLM, conf=0.82)

  cites [57] Lood, C. et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med. 22, 146–153 (2016). sourceExperimental — accuracy not yet measured

In the paper

“In the absence of active caspases, mtDNA released following mitochondrial outer membrane permeabilization triggers type I interferon responses in a cGAS–STING-dependent manner143,144”

What the sources say

• Supported

  The Results sections on mtDNA-dependent type I IFN expression and cGAS/STING activation report that Bax/Bak-mediated mitochondrial permeabilization releases mtDNA, which induces type I IFN when caspase activity is absent. They also report that loss of either cGAS or STING prevents the IFN response. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites [143] Rongvaux, A. et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell 159, 1563–1577 (2014). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction identifies Bak/Bax as the drivers of mitochondrial outer membrane permeabilization. The Results show that, when apoptotic caspases are inhibited, mitochondrial DNA is required for IFN-β production and that loss of cGAS or STING prevents it. No page numbers are available in our copy. (LLM, conf=0.94)

  cites [144] White, M. J. et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159, 1549–1562 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Abnormal retention of mitochondria in mature erythrocytes in patients with SLE is caused by a defective hypoxia-inducible factor (HIF)-mediated metabolic switch that leads to impaired activation of the ubiquitin-proteasome system, necessary for the execution of mitophagy during human erythroid cell maturation”

What the sources say

• Supported

  The Introduction states that a defect in the HIF-mediated metabolic switch prevents UPS activation and mitophagy, resulting in mitochondria-containing RBCs in SLE. The Results section, “Impaired HIF-2α-mediated metabolic switch and UPS activation in SLE erythroblasts,” links that defect to mitochondrial retention in mature RBCs. (LLM, conf=0.94)

  cites [119] Caielli, S. et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 184, 4464–4479 e4419 (2021). source

In the paper

“mtDNA or mtRNA released into the cytosol via BAX–BAK macropores can activate nucleic acid sensors in the cytosol145 independently of cell death130,146,147, ultimately leading to the production of type I interferon”

What the sources say

• Partly supported

  The Results section (‘Mitochondria, not EVs stimulate a strong IL6 response’; page unavailable) reports mitochondrial cargo in extracellular vesicles when cell death was kept below 5%, and an IP10 response to those vesicles. This supports an inflammatory response without substantial cell death, but the paper does not establish release of mtDNA or mtRNA into the cytosol through BAX–BAK macropores, activation of cytosolic nucleic-acid sensors, or resulting type I interferon production. (LLM, conf=0.79)

  cites [145] Todkar, K. et al. Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs. Nat. Commun. 12, 1971 (2021). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [130] McArthur, K. et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science 359, eaao6047–eaao6047 (2018). source
• Partly supported

  The Results and Discussion report that IL-1β induces cytosolic mtDNA release without detectable cell death, followed by cGAS–STING signaling and IFNB1 induction (pages not provided). The paper does not establish release through BAX–BAK macropores or show that mtRNA drives this response; its Discussion says the mechanism of mtDNA release remains unknown. (LLM, conf=0.88)

  cites [146] Aarreberg, L. D. et al. Interleukin-1β induces mtDNA release to activate innate immune signaling via cGAS-STING. Mol. Cell 74, 801–815.e6 (2019). sourceExperimental — accuracy not yet measured
• Supported

  For the clause marked by citation 145, the paper reports that cytosolic mtDNA engages the DNA sensor cGAS. Its main text (indexed under Abstract; page unavailable) and Extended Data Figure 8 link this sensing pathway to potentiated type I interferon responses. The separate claims about BAX–BAK macropores and independence from cell death carry other citations in the citing sentence. (LLM, conf=0.91)

  cites [147] West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553–557 (2015). source

In the paper

“high interferon-stimulated gene signatures in patients with SLE are associated with the presence of mitochondria-containing erythrocytes and opsonizing antibodies119”

What the sources say

• Supported

  The Results section reports higher ISG transcriptional activity in SLE patients with both mitochondria-containing red blood cells and opsonizing serum. The Discussion likewise states that their concomitant presence correlates with an enhanced blood ISG signature. (LLM, conf=0.95)

  cites [119] Caielli, S. et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 184, 4464–4479 e4419 (2021). source

In the paper

“Consistently, depletion of BAX and BAK proteins or inhibition of BAX oligomerization in these cells leads to a considerable decrease in mtDSB-induced type I interferon response.”

What the sources say

• Supported

  The main text reports a striking reduction in interferon-stimulated gene transcription after mtDSBs in BAX/BAK double-knockout cells compared with wild-type cells. It says a BAX peptide inhibitor that blocks oligomerization corroborated the result; the Fig. 3 legend identifies the measured genes as RSAD2 and ISG15. (LLM, conf=0.94)

  cites [149] Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y. & Sfeir, A. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature 591, 477–481 (2021). source

In the paper

“in peripheral blood mononuclear cells, the level of VDAC oligomers and cytosolic mtDNA is higher in patients with SLE than in healthy individuals”

What the sources say

• Partly supported

  The passage discussing Fig. 4B reports more VDAC1 oligomers in PBMCs from patients with SLE than in healthy controls. It reports elevated cytosolic mtDNA in splenocytes from lupus-prone mice, not in human PBMCs; the latter part of the claim is therefore unsupported. (LLM, conf=0.88)

  cites [148] Kim, J. et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 366, 1531–1536 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Notably, mtDNA double-stranded breaks (mtDSBs) generated by mitochondria-targeted nucleases or irradiation can trigger cytosolic leakage of mtRNA and induce retinoic acid-inducible gene I (RIGI)-dependent interferon responses in human epithelial cells149.”

What the sources say

• Supported

  The paper’s main text (page not provided) reports that mitochondria-targeted nucleases cause mtDNA breaks followed by cytoplasmic mtRNA release and a RIG-I/MAVS-dependent interferon response. It also reports cytoplasmic mtRNA enrichment and substantially reduced RIG-I-dependent immune activation after irradiation. The authors caution that irradiation may engage RNA sensing through other forms of damage as well. (LLM, conf=0.89)

  cites [149] Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y. & Sfeir, A. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature 591, 477–481 (2021). source

In the paper

“This well-controlled process, involving the selective packaging of mitochondrial proteins in these vesicles, prevents their release as mtDAMPs by cells145”

What the sources say

• Supported

  The Introduction states that cells selectively regulate the packaging of mitochondrial proteins into extracellular vesicles, preventing the release of damaged components that would act as pro-inflammatory DAMPs. It also explains that mitochondria-derived vesicles direct damaged components toward lysosomal degradation rather than extracellular release. (LLM, conf=0.92)

  cites [145] Todkar, K. et al. Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs. Nat. Commun. 12, 1971 (2021). source

In the paper

“phagocytosis of opsonized mitochondria-containing erythrocytes induces activation of the DNA-sensing cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway in macrophages and induces subsequent production of type I interferons119”

What the sources say

• Supported

  The Results section reports that macrophages engulfing opsonized mitochondria-containing RBCs produced more IFNα than those engulfing opsonized mitochondria-negative RBCs. In the same subsection, knockdown of cGAS or STING1 largely abrogated the downstream response, supporting the attributed pathway. Page numbers were not supplied. (LLM, conf=0.94)

  cites [119] Caielli, S. et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 184, 4464–4479 e4419 (2021). source

In the paper

“Oxidized mtDNA released from neutrophils of patients with SLE can induce type I interferon production by plasmacytoid dendritic cells175”

What the sources say

• Supported

  The Abstract states that activated lupus neutrophils release oxidized mtDNA bound to TFAM, which induces high levels of IFN-α in plasmacytoid dendritic cells. The Discussion also describes the released oxidized mtDNA as a potent pDC activator. (LLM, conf=0.95)

  cites [175] Caielli, S. et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 213, 697–713 (2016). source

In the paper

“Furthermore, mitochondrial fMet peptide-mediated signalling is a potential therapeutic target for ameliorating neutrophil-dominant inflammation in sterile inflammatory conditions such as RA185.”

What the sources say

• Supported

  The Discussion proposes mtNFP-mediated signaling as a potential therapeutic target in RA. The Conclusion identifies FPR signaling in sterile injury and chronic inflammatory conditions such as RA as a therapeutic target for ameliorating neutrophil-dominant inflammation. (LLM, conf=0.95)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“Notably, mitochondrial fMet peptides circulating in the plasma of patients with RA can support neutrophil activation in vitro via FPR1 (as shown by FPR1 blockade experiments)185.”

What the sources say

• Supported

  The Discussion reports that RA plasma induced ROS production in healthy-donor neutrophils and that FPR1 blockade suggested circulating mtNFPs contributed significantly to this activation. The Methods also identify cyclosporine H as the FPR1 inhibitor used in the neutrophil activation assays. (LLM, conf=0.94)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“Specifically, increased levels of mitochondrial fMet peptides, as has been observed in three independent cohorts of patients with RA, correlate with circulating levels of neutrophil activation markers, including levels of NETs, calprotectin and peroxidase, as well as with markers of inflammation (such as C-reactive protein (CRP) level and erythrocyte sedimentation rate).”

What the sources say

• Supported

  The Results section reports elevated total fMet levels in all three RA cohorts compared with healthy controls. It also reports significant associations between circulating mtNFPs and calprotectin, NETs, and peroxidase across the three cohorts, plus correlations with CRP and ESR; the latter were reported in specified cohorts, not necessarily all three. (LLM, conf=0.94)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“Some of the factors involved in priming these neutrophils could include TNF and LPS, which are known to upregulate the expression of FPR1 on neutrophils181–183.”

What the sources say

• ?Not checked — no full text of the sourcecites [181] O’Flaherty, J. T., Rossi, A. G., Redman, J. F. & Jacobson, D. P. Tumor necrosis factor-α regulates expression of receptors for formyl-methionyl-leucyl-phenylalanine, leukotriene B4, and platelet-activating factor. Dissociation from priming in human polymorphonuclear neutrophils. J. Immunol. 147, 3842–3847 (1991). source
• Partly supported

  The section “LPS induces FPR1 mRNA via transcriptional and posttranscriptional mechanisms” (page not supplied) reports increased FPR1 mRNA in mouse neutrophils after LPS treatment. The cytokine experiments (Fig. 7; page not supplied) show that TNF-α increased FPR1 mRNA in macrophages, not neutrophils. The paper therefore supports the LPS portion but does not establish that TNF upregulates FPR1 in neutrophils or directly demonstrate neutrophil priming. (LLM, conf=0.87)

  cites [182] Mandal, P., Novotny, M. & Hamilton, T. A. Lipopolysaccharide induces formyl peptide receptor 1 gene expression in macrophages and neutrophils via transcriptional and posttranscriptional mechanisms. J. Immunol. 175, 6085–6091 (2005). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [183] Hirotani, T. et al. Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-β. Biochem. Biophys. Res. Commun. 328, 383–392 (2005). source

In the paper

“Notably, data from animal models of septic arthritis have shown that bacteria-derived fMet peptides are virulence factors that contribute to joint damage via neutrophil-mediated inflammation in the joints184.”

What the sources say

• Supported

  The Conclusions (p. 1) explicitly identify bacterial formylated peptides as virulence factors in mouse S. aureus arthritis and say they contribute to joint damage partly by recruiting neutrophils. The Discussion (p. 6) also reports greater joint destruction and neutrophil infiltration with the formyl-peptide-producing strain. (LLM, conf=0.94)

  cites [184] Gjertsson, I., Jonsson, I. M., Peschel, A., Tarkowski, A. & Lindholm, C. Formylated peptides are important virulence factors in Staphylococcus aureus arthritis in mice. J. Infect. Dis. 205, 305–311 (2012). source

In the paper

“Overall, these findings suggest that mitochondrial fMet peptides might be useful novel clinical biomarkers for measuring disease activity and disease severity.”

What the sources say

• Supported

  The Discussion explicitly proposes mtNFPs as novel clinical biomarkers for measuring disease activity and severity in rheumatoid arthritis. The claim preserves that proposal’s tentative nature. (LLM, conf=0.95)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“Additionally, the presence of extracellular cytochrome c and markers of oxidative stress in joints and connective tissues of patients with psoriasis or psoriatic arthritis suggests that mitochondrial dysfunction has a role in inflammatory arthritis210.”

What the sources say

• Partly supported

  The Conclusions (page unavailable) say that oxidative stress and inflammation in psoriasis and psoriatic arthritis may lead to cytochrome c release into extracellular space. The section on oxidative stress in psoriatic arthritis reports mitochondrial DNA mutations and oxidative-stress findings in joint synovial cells. The paper does not establish that extracellular cytochrome c was detected in patients’ joints or connective tissues; it discusses circulating or serum cytochrome c instead. (LLM, conf=0.87)

  cites [210] Chimenti, M. S. et al. Potential role of cytochrome c and tryptase in psoriasis and psoriatic arthritis pathogenesis: focus on resistance to apoptosis and oxidative stress. Front. Immunol. https://doi.org/10.3389/fimmu.2018.02363 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Thus, mitochondria are the only cellular compartment to produce and sequester endogenous N-formylated (fMet) peptides.”

What the sources say

• Partly supported

  The discussion (p. 762) says formylated f-Met-tRNA is found exclusively in mitochondria and that mitochondrial-specific protein synthesis is likely intramitochondrial. It does not establish that N-formylated peptides themselves are produced only there or sequestered there; those claims go beyond its findings in HeLa cells. (LLM, conf=0.83)

  cites [176] Galper, J. B. Mitochondrial protein synthesis in HeLa cells. J. Cell Biol. 60, 755–763 (1974). sourceExperimental — accuracy not yet measured

In the paper

“Cardiolipin is also involved in the regulation of mitochondrial fusion and fission191–193.”

What the sources say

• ?Not checked — no full text of the sourcecites [191] Ban, T. et al. Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin. Nat. Cell Biol. 19, 856–863 (2017). source
• Supported

  The Introduction (page not indicated) identifies Opa1 as a mitochondrial fusion protein and says cardiolipin stimulates the activity of Opa1 and Mgm1. The Conclusions (page not indicated) report a functional interaction between cardiolipin and Drp1, the mitochondrial fission protein. Together, these support the broad claim that cardiolipin is involved in regulating fusion and fission. (LLM, conf=0.88)

  cites [192] Bustillo-Zabalbeitia, I. et al. Specific interaction with cardiolipin triggers functional activation of dynamin-related protein 1. PLoS One 9, e102738 (2014). sourceExperimental — accuracy not yet measured
• ?Could not verify

  Section 2 discusses cardiolipin’s role in organizing mitochondrial membrane domains and respiratory protein complexes, while Section 5 discusses membrane assembly. Neither addresses regulation of mitochondrial fusion or fission; searches for those processes and mitochondrial dynamics found no relevant passage in our copy. (LLM, conf=0.72)

  cites [193] Schlame, M. & Ren, M. The role of cardiolipin in the structural organization of mitochondrial membranes. Biochim. Biophys. Acta 1788, 2080–2083 (2009). sourceExperimental — accuracy not yet measured

In the paper

“reports suggest that cytochrome c can bind to leucine-rich α2 glycoprotein, a plasma protein that is elevated during inflammation206,207.”

What the sources say

• Supported

  The Results and discussion section (“Possible physiological function of LRG”; page unavailable) reports that LRG binds strongly to cytochrome c. The abstract identifies LRG as a plasma protein, and the mouse endotoxemia discussion reports increased serum LRG in patients with bacterial infections. These passages support the hedged claim. (LLM, conf=0.91)

  cites [206] Shirai, R., Hirano, F., Ohkura, N., Ikeda, K. & Inoue, S. Up-regulation of the expression of leucine-rich α2-glycoprotein in hepatocytes by the mediators of acute-phase response. Biochem. Biophys. Res. Commun. 382, 776–779 (2009). source
• Supported

  The Introduction describes LRG1 as a serum protein whose levels increase in bacterial infections and inflammatory disorders, and states that it has been reported to bind cytochrome c. The Results section also reports that neutrophil-derived LRG1 bound to a cytochrome c affinity column. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites [207] Druhan, L. J. et al. Leucine rich α-2 glycoprotein: a novel neutrophil granule protein and modulator of myelopoiesis. PLoS One 12, e0170261 (2017). source

In the paper

“Moreover, programmed necrosis (known as necroptosis) and pyroptosis induce the active release of intact mitochondria into the extracellular milieu211.”

What the sources say

• Partly supported

  The section “Rupture of Pyroptotic Cells Releases Macro-DAMPs and Is” (page unavailable) reports mitochondrial DNA and CoxI in supernatants after pyroptotic cells were ruptured by pipetting, and says mitochondrial release from necroptotic cells had been reported. It does not establish that either process actively releases intact mitochondria; its pyroptosis finding depends on cell rupture induced by external shear stress. (LLM, conf=0.88)

  cites [211] Davis, M. A. et al. Calpain drives pyroptotic vimentin cleavage, intermediate filament loss, and cell rupture that mediates immunostimulation. Proc. Natl Acad. Sci. USA 116, 5061–5070 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Furthermore, during early apoptosis, cytochrome c undergoes conformational changes owing to interactions with cardiolipin, contributing to the subsequent cytosolic release of cytochrome c and caspase activation194.”

What the sources say

• Supported

  The “Structural Change Dictates New Function” section says cardiolipin binding changes cytochrome c’s structure and enables peroxidase activity, an early step in apoptosis. It links that activity to cytosolic cytochrome c release and subsequent caspase activation. (LLM, conf=0.90)

  cites [194] Muenzner, J. & Pletneva, E. V. Structural transformations of cytochrome c upon interaction with cardiolipin. Chem. Phys. Lipids 179, 57–63 (2014). source

In the paper

“Furthermore, the mitochondrial fMet levels at baseline are predictive of extra-articular nodules development.”

What the sources say

• Supported

  The Results section (“Levels of mtNFPs (total fMet levels) associate with disease progression in combination with ACPA”) explicitly reports that baseline mtNFP levels predicted extra-articular nodule development in an RA inception cohort (OR=1.2 per 10 ng/ml, p=0.04). The paper identifies these mtNFP measurements as total fMet levels. (LLM, conf=0.94)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“In this disease, neutrophils are primed to respond to fMet peptides, as shown by the high oxidative burst of neutrophils in response to fMLP, a prototypic bacterial fMet peptide, ex vivo180.”

What the sources say

• Supported

  The Abstract reports greater FMLP-induced superoxide production by RA blood and synovial-fluid neutrophils than by control blood neutrophils, and concludes that circulating RA neutrophils appear ready to respond to inflammatory stimulation. The blood-neutrophil comparison section specifies that the difference was detected at the tested FMLP concentration, not at every concentration. Page numbers are not supplied in the excerpts. (LLM, conf=0.92)

  cites [180] Eggleton, P., Wang, L., Penhallow, J., Crawford, N. & Brown, K. A. Differences in oxidative response of subpopulations of neutrophils from healthy subjects and patients with rheumatoid arthritis. Ann. Rheum. Dis. 54, 916–923 (1995). source

In the paper

“The synthesis of mitochondrial protein is initiated by an N-formylmethionyl-tRNA, similar to that which occurs in prokaryotes176.”

What the sources say

• Partly supported

  The Abstract (p. 755) says experiments support N-formylmethionyl-tRNA as the initiator of mitochondrial protein synthesis in HeLa cells. The Discussion (pp. 761–762) describes synthesis as appearing to be initiated this way and draws a parallel with prokaryotic ribosomes. The citing sentence states initiation as settled fact, whereas the paper presents it as a supported inference. (LLM, conf=0.86)

  cites [176] Galper, J. B. Mitochondrial protein synthesis in HeLa cells. J. Cell Biol. 60, 755–763 (1974). sourceExperimental — accuracy not yet measured

In the paper

“Incorporating measurements of mitochondrial fMet level can improve the prognostic capacity of ACPA positivity to predict erosive disease in RA.”

What the sources say

• Supported

  The Results section, “Levels of mtNFPs (total fMet levels) associate with disease progression in combination with ACPA,” directly tests whether fMet improves ACPA’s prognostic value for erosive disease in RA. It reports higher odds for ACPA or fMet positivity than for ACPA positivity alone (OR 7.9 versus 5.7). Page numbers were not provided in our copy. (LLM, conf=0.94)

  cites [185] Duvvuri, B. et al. Mitochondrial N-formyl methionine peptides associate with disease activity as well as contribute to neutrophil activation in patients with rheumatoid arthritis. J. Autoimmun. 119, 102630 (2021). source

In the paper

“They contrast with polyreactive aCL antibodies that require the presence of protein–phospholipid complexes such as those containing β2 glycoprotein I (β2GPI, also known as apolipoprotein H)248–250.”

What the sources say

• ?Not checked — no full text of the sourcecites [248] Rauch, J., Tannenbaum, H., Stollar, B. D. & Schwartz, R. S. Monoclonal anti-cardiolipin antibodies bind to DNA. Eur. J. Immunol. 14, 529–534 (1984). source
• ?Could not verify

  The Materials and Methods (page unavailable) describe separate cardiolipin and β2GPI ELISA coatings, while the Results report aCL and anti-β2GPI antibodies separately. Searches for polyreactivity, protein–phospholipid complexes, and a requirement for β2GPI found no passage in the paper’s discussion or findings establishing the claimed requirement; a cited work’s title in the References is not itself a finding of this paper. (LLM, conf=0.75)

  cites [249] Oaks, Z. et al. Mitochondrial dysfunction in the liver and antiphospholipid antibody production precede disease onset and respond to rapamycin in lupus-prone mice. Arthritis Rheumatol. 68, 2728–2739 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [250] McNeil, H. P., Simpson, R. J., Chesterman, C. N. & Krilis, S. A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H). Proc. Natl Acad. Sci. USA 87, 4120–4124 (1990). source

In the paper

“Molecular mimicry might also explain the antigenicity of some mitochondrial proteins and their presentation by MHC II molecules227”

What the sources say

• Partly supported

  Section 8 proposes that mitochondrial peptides presented with class II HLA could mimic microbial or self-peptides and trigger an autoimmune response. Section 7.1 likewise discusses mimicry involving peptides bound to MHC class II. These passages support a possible explanation for antigenicity, but treat class II presentation as a condition for mimicry, not something mimicry itself explains. (LLM, conf=0.82)

  cites [227] Baum, H. Mitochondrial antigens, molecular mimicry and autoimmune disease. Biochim. Biophys. Acta 1271, 111–121 (1995). sourceExperimental — accuracy not yet measured

In the paper

“Notably, stimulated monocytes also release extracellular mitochondria capable of stimulating the production of pro-inflammatory cytokines by endothelial cells219”

What the sources say

• Supported

  The Discussion states that LPS-activated monocytic cells release free mitochondria that can activate endothelial cells. The section on mitochondria released by or isolated from LPS-activated cells reports that mitochondria from activated cells induced endothelial IL-8 production, supporting the claim about pro-inflammatory cytokine production. (LLM, conf=0.93)

  cites [219] Puhm, F. et al. Mitochondria are a subset of extracellular vesicles released by activated monocytes and induce type I IFN and TNF responses in endothelial cells. Circ. Res. 125, 43–52 (2019). source

In the paper

“Positivity for polyreactive aCL antibodies is a criterion in the classification of two autoimmune conditions: APS and SLE251,252.”

What the sources say

• Partly supported

  The SLE classification-criteria figure lists anti-cardiolipin antibodies as a weighted antiphospholipid-antibody criterion, alongside other requirements for classifying SLE (page not supplied in our copy). It does not specify polyreactive aCL antibodies. This paper sets out SLE criteria, not APS criteria; the sentence also cites another source for APS. (LLM, conf=0.86)

  cites [251] Aringer, M. et al. European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol. 78, 1151–1159 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  The 'Update of the classification criteria' section identifies persistent, medium- or high-titer IgG or IgM aCL positivity as an APS laboratory criterion, with a specified positivity threshold. It does not identify polyreactivity as a criterion or establish aCL positivity as an SLE classification criterion; the SLE portion of the citing sentence may be supported by its other citation, but not by this paper. (LLM, conf=0.84)

  cites [252] Miyakis, S. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 4, 295–306 (2006). sourceExperimental — accuracy not yet measured

In the paper

“Importantly, the intact mitochondria released during necroptosis can trigger pro-inflammatory responses following engulfment by other immune cells212.”

What the sources say

• Supported

  The Discussion reports that mitochondria released during TNF-α-induced necroptosis were intact and that human macrophages and dendritic cells engulfed them. It also reports that macrophage uptake triggered TNF-α secretion, supporting the claimed pro-inflammatory response. Page numbers were not provided. (LLM, conf=0.94)

  cites [212] Maeda, A. & Fadeel, B. Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals. Cell Death Dis. 5, e1312 (2014). source

In the paper

“aCL antibody titres in these diseases are associated with thrombosis and pregnancy complications253.”

What the sources say

• Partly supported

  The Introduction (page not available) links antiphospholipid antibodies in lupus and APS to thrombotic and obstetric complications, and identifies anticardiolipin positivity in patients with recurrent thrombosis. It does not establish that anticardiolipin antibody titres, specifically, are associated with both thrombosis and pregnancy complications. (LLM, conf=0.85)

  cites [253] Vreede, A. P., Bockenstedt, P. L. & Knight, J. S. Antiphospholipid syndrome: an update for clinicians and scientists. Curr. Opin. Rheumatol. 29, 458–466 (2017). sourceExperimental — accuracy not yet measured

In the paper

“The hydrolysis of mitochondrial membranes by secreted phospholipase A2 group IIA results in the release of pro-inflammatory lipid mediators and mtDNA, which promote neutrophil activation215.”

What the sources say

• Supported

  The Results report that sPLA2-IIA hydrolyzes mitochondrial membranes, releasing pro-inflammatory lipids and mtDNA. They also show that neutrophils produce abundant leukotriene B4 when extracellular mitochondria and catalytically active sPLA2-IIA are present. The claim is consistent with those findings. (LLM, conf=0.91)

  cites [215] Boudreau, L. H. et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 124, 2173–2183 (2014). source

In the paper

“In a similar fashion, numerous stimuli, including immune complexes and their combination with TLR ligands, are able to induce platelet activation and subsequent release of extracellular mitochondria214,215.”

What the sources say

• ?Not checked — no full text of the sourcecites [214] Melki, I. et al. Platelets release mitochondrial antigens in systemic lupus erythematosus. Sci. Transl. Med. 13, eaav5928–eaav5928 (2021). source
• Partly supported

  The Results report that thrombin and other tested platelet stimuli led to the release of extracellular mitochondria. Our copy does not establish that immune complexes, alone or combined with TLR ligands, were among those stimuli; searches for those terms found no such result. (LLM, conf=0.86)

  cites [215] Boudreau, L. H. et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 124, 2173–2183 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Deletion of β2 microglobulin (an MHC class I molecule) or CD1d (a non-classical MHC protein) in an NZW/NZB F1 murine model of spontaneous SLE results in a reduction of circulating aCL antibodies223,224.”

What the sources say

• Supported

  The Abstract (Results) reports lower serum anti-cardiolipin (anti-CL) antibody levels in both β2m-deficient and CD1d-deficient BWF1 mice than in control littermates. The Results sections on anti-CL antibodies report the same finding; page numbers were not supplied. (LLM, conf=0.94)

  cites [223] Singh, R. R., Yang, J. Q., Kim, P. J. & Halder, R. C. Germline deletion of β2 microglobulin or CD1d reduces anti-phospholipid antibody, but increases autoantibodies against non-phospholipid antigens in the NZB/W F1 model of lupus. Arthritis Res. Ther. 15, R47 (2013). source
• ?Could not verify

  The Results section on CD1d-restricted γδ T-cell responses reports experiments in C57BL/6 mice measuring responses to cardiolipin, not circulating anti-cardiolipin antibodies. The Discussion mentions lupus only as a possible setting for these T-cell responses. Searches for β2 microglobulin deletion, NZW/NZB F1 mice, and circulating aCL antibodies found no passage addressing the claimed reduction. (LLM, conf=0.76)

  cites [224] Dieudé, M. et al. Cardiolipin binds to CD1d and stimulates CD1d-restricted γδ T cells in the normal murine repertoire. J. Immunol. 186, 4771–4781 (2011). sourceExperimental — accuracy not yet measured

In the paper

“however, later studies confirmed that AMA-M5 and antiphospholipid antibodies (aPL; a group comprising lupus anticoagulant, anti-β2GPI antibodies and aCL antibodies) are distinct autoantibodies254,255.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [254] Labro, M. T., Andrieu, M. C., Weber, M. & Homberg, J. C. A new pattern of non-organ- and non-species-specific anti-organelle antibody detected by immunofluorescence: the mitochondrial antibody number 5. Clin. Exp. Immunol. 31, 357–366 (1978).
• Supported

  The Discussion states that this study confirmed the association of AMA M5 with lupus anticoagulant, anti-cardiolipin and anti-β2-GPI antibodies while demonstrating that they belong to separate antibody populations. The Results also report evidence that AMA M5 and anti-β2-GPI reactivities came from different antibody populations. (LLM, conf=0.94)

  cites [255] La Rosa, L. et al. Anti-mitochondrial M5 type antibody represents one of the serological markers for anti-phospholipid syndrome distinct from anti-cardiolipin and anti-β2-glycoprotein I antibodies. Clin. Exp. Immunol. 112, 144–151 (1998). source

In the paper

“The release of extracellular mitochondria with preserved functions and their subsequent recapture by other cells might enable the restoration of mitochondrial functions in the recipient cells33,280–282.”

What the sources say

• ?Could not verify

  The Introduction describes mitochondrial function and cybrids made by fusing cells with mitochondrial donors, but not the release and recapture of extracellular mitochondria. Searches for extracellular mitochondria, intercellular transfer, and restoration of recipient-cell function found no passage addressing the claim. (LLM, conf=0.76)

  cites [33] Sun, D., Wei, Y., Zheng, H. X., Jin, L. & Wang, J. Contribution of mitochondrial DNA variation to chronic disease in East Asian populations. Front. Mol. Biosci. 6, 128 (2019). sourceExperimental — accuracy not yet measured
• Supported

  The section on mitochondrial transfer for intercellular degradation reports that mitochondria extruded by stressed cells were taken up and reused by recipient macrophages, enhancing their bioenergetics. The mechanisms section also reports that internalized healthy mitochondria can restore recipients’ oxidative phosphorylation and bioenergetics, while noting that evidence for physiological release and uptake of intact free mitochondria is relatively weak. The citing sentence’s “might” is consistent with that limitation; page numbers are unavailable in our copy. (LLM, conf=0.86)

  cites [280] Liu, D. et al. Intercellular mitochondrial transfer as a means of tissue revitalization. Signal. Transduct. Target. Ther. 6, 65 (2021). source
• Supported

  Section 4, “Mechanisms of mitochondrial transfer” (page not specified), describes mitochondria-containing microvesicles released by donor cells, engulfed by recipient alveolar epithelial cells, and followed by increased epithelial ATP production. Section 2, “Mitochondrial transfer in organs” (page not specified), also reports uptake of functionally active isolated mitochondria. Together these support the claim’s hedged account of functional restoration after extracellular transfer and uptake. (LLM, conf=0.90)

  cites [281] Sinha, P., Islam, M. N., Bhattacharya, S. & Bhattacharya, J. Intercellular mitochondrial transfer: bioenergetic crosstalk between cells. Curr. Opin. Genet. Dev. 38, 97–101 (2016). source
• Supported

  The Extracellular vesicles section (page unavailable) says vesicles can carry full functional mitochondria and that recipient cells may acquire whole mitochondrial particles through vesicles, most likely rescuing mitochondrial function. The paper presents this as a likely mechanism, consistent with the claim’s “might.” (LLM, conf=0.90)

  cites [282] Torralba, D., Baixauli, F. & Sanchez-Madrid, F. Mitochondria know no boundaries: mechanisms and functions of intercellular mitochondrial transfer. Front. Cell Dev. Biol. 4, 107 (2016). source

In the paper

“The balance between glycolysis and oxidative phosphorylation in providing energy for the cell not only defines the yield of ATP production but might also affect the levels of oxidation (for example, through the production of mtROS) and the consumption of metabolites (such as glucose and fatty acids)273,274.”

What the sources say

• Partly supported

  The Respiratory chain section (page unavailable) says oxidative phosphorylation retains energy in ATP, and the Reactive oxygen species section (page unavailable) says cellular respiration produces mitochondrial ROS. The copy does not say that the balance between glycolysis and oxidative phosphorylation determines ATP yield or affects oxidation levels and consumption of glucose or fatty acids. (LLM, conf=0.83)

  cites [273] Tokarska, K., Majsterek, I., Cuchra, M. & Wozniacka, A. Immunometabolic disorders in the pathogenesis of systemic lupus erythematosus. Postepy Dermatol. Alergol. 36, 513–518 (2019). sourceExperimental — accuracy not yet measured
• Supported

  The section on RA CD4 T cells shunting glucose toward the pentose phosphate pathway links glucose allocation to ATP production, mitochondrial activity and ROS levels. The section on lipid droplets adds that suppressed mitochondrial activity reduces ATP and ROS generation and prevents fatty-acid oxidation. Together, these passages support the citing sentence’s hedged point; the paper discusses it chiefly in RA T cells. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [274] Weyand, C. M. & Goronzy, J. J. Immunometabolism in the development of rheumatoid arthritis. Immunol. Rev. 294, 177–187 (2020). source

In the paper

“Given the bacterial features of mitochondria, the detection of mitochondrial motives by cells of the innate and adaptive immunity might elicit potent pro-inflammatory responses147,276,277.”

What the sources say

• Partly supported

  The paper’s Abstract reports that cytosolic mitochondrial DNA engages an innate immune sensor and potentiates type I interferon responses. It does not establish detection by adaptive immune cells or a broad, potent pro-inflammatory response; the demonstrated response is specifically antiviral innate signaling. The indexed passages provide no page number. (LLM, conf=0.85)

  cites [147] West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553–557 (2015). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction discusses immune responses to bacterial CpG motifs and to DNA-containing immune complexes, but it does not address mitochondrial motifs or their detection by innate and adaptive immune cells. Searches for mitochondrial DNA, mitochondria, and mitochondrial motifs found no passage supporting the attributed claim. The available passages have no page numbers. (LLM, conf=0.75)

  cites [276] Pisetsky, D. S., Gauley, J. & Ullal, A. J. Microparticles as a source of extracellular DNA. Immunol. Res. 49, 227–234 (2011). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction describes mitochondria’s bacterial ancestry, and “Mitochondrial Defects Cause Diverse and Complex Human Diseases” says that the innate immune system recognizes and targets mouse cells with allogenic mtDNA. Our copy does not say that adaptive immunity detects mitochondrial motifs or that such detection elicits potent pro-inflammatory responses. (LLM, conf=0.82)

  cites [277] Nunnari, J. & Suomalainen, A. Mitochondria: in sickness and in health. Cell 148, 1145–1159 (2012). sourceExperimental — accuracy not yet measured

In the paper

“In addition to the release of mitochondria (as free organelle or encapsulated in extracellular vesicles) and their capture by recipient cells, the transfer of mitochondria between cells might occur via cellular fusion or tunnelling nanotubes283–285.”

What the sources say

• ?Not checked — no full text of the sourcecites [283] Rustom, A., Saffrich, R., Markovic, I., Walther, P. & Gerdes, H. H. Nanotubular highways for intercellular organelle transport. Science 303, 1007–1010 (2004). source
• Partly supported

  Section 5 says mitochondrial transfer from a donor cell can occur through nanotubes, supporting that route. It does not describe transfer through cellular fusion: its discussion of fusion concerns exogenous mitochondria joining the recipient cell’s mitochondrial network after uptake, not the fusion of two cells. No page number is available in our copy. (LLM, conf=0.87)

  cites [284] Miliotis, S., Nicolalde, B., Ortega, M., Yepez, J. & Caicedo, A. Forms of extracellular mitochondria and their impact in health. Mitochondrion 48, 16–30 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction says mitochondrial transfer can occur via tunneling nanotubes, and the Results describe cell-contact-dependent transfer between hematopoietic progenitors and bone marrow stromal cells. Neither passage identifies cellular fusion as a transfer mechanism, so the source supports only the nanotube part of the claim. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [285] Golan, K. et al. Bone marrow regeneration requires mitochondrial transfer from donor Cx43-expressing hematopoietic progenitors to stroma. Blood 136, 2607–2619 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Research into the active release of mitochondria into the extracellular milieu212,214,278 has led to the discovery of a new type of cell-to-cell communication, termed ‘transmitophagy’, that contributes to both inflammation and tissue rejuvenation.”

What the sources say

• Supported

  The citation follows the clause about active release of mitochondria into the extracellular milieu. The Discussion states that mitochondria are released before plasma-membrane disruption, indicating an active process. The later claim about transmitophagy is not the part to which this citation is attached. (LLM, conf=0.91)

  cites [212] Maeda, A. & Fadeel, B. Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals. Cell Death Dis. 5, e1312 (2014). source
• ?Not checked — no full text of the sourcecites [214] Melki, I. et al. Platelets release mitochondrial antigens in systemic lupus erythematosus. Sci. Transl. Med. 13, eaav5928–eaav5928 (2021). source
• ?Not checked — no full text of the sourcecites [278] Marcoux, G. et al. Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. Platelets 28, 272–280 (2017). source

In the paper

“Antibodies to mitochondrial nucleic acids (mtDNA and mtRNA) are also present in patients with SLE or APS230,231,261,262.”

What the sources say

• Partly supported

  The Results (Figure 4; page not provided) report elevated anti-mtDNA antibodies in SLE patients, but not in the APS patients tested. The paper does not report antibodies to mtRNA, so it supports only the SLE/mtDNA part of the claim. (LLM, conf=0.90)

  cites [230] Becker, Y. et al. Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations. Sci. Rep. 9, 4530 (2019). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction (page not provided) states that anti-mtDNA antibodies were found in SLE patients and describes anti-mtRNA antibodies in SLE and APS. The Results (page not provided) report elevated anti-mtRNA antibodies in both patient groups. The paper does not establish anti-mtDNA antibodies in APS, but the claim does not require both antibodies to occur in both conditions. (LLM, conf=0.92)

  cites [231] Becker, Y. et al. Autoantibodies in systemic lupus erythematosus target mitochondrial RNA. Front. Immunol. 10, 1026 (2019). source
• ?Not checked — no full text of the sourcecites [261] Becker, Y. L., Julien, A. S., Godbout, A., Boilard, E. & Fortin, P. R. Pilot study of anti-mitochondrial antibodies in antiphospholipid syndrome. Lupus 29, 1623–1629 (2020). source
• Partly supported

  The Discussion (page unavailable) reports anti-DNA and anti-whole-mitochondrion reactivity in SLE patients, but says the DNA target could be mitochondrial, nuclear, or a cross-reactive antigen. The paper does not establish antibodies specifically to mtDNA or mtRNA, and it does not report findings in APS patients. (LLM, conf=0.86)

  cites [262] Pisetsky, D. S. et al. The binding of SLE autoantibodies to mitochondria. Clin. Immunol. 212, 108349 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Using mass spectrometry, researchers have attempted to identify the mitochondrial targets of these autoantibodies: in this study, 431 mitochondrial proteins (and hence potential targets) co-precipitated with autoantibodies from patients with SLE266.”

What the sources say

• Supported

  The Methods report that shotgun proteomic profiling identified 431 proteins associated with the mitochondrial proteome. The Figure 1 caption describes affinity purification using IgG from patients with SLE followed by mass spectrometry, supporting the claim that these were co-isolated proteins and potential targets, not necessarily validated targets. (LLM, conf=0.93)

  cites [266] Becker, Y. L. et al. Identification of mitofusin 1 and complement component 1q subcomponent-binding protein as mitochondrial targets in systemic lupus erythematosus. Arthritis Rheumatol. https://doi.org/10.1002/art.42082 (2022). source

In the paper

“Among these targets, autoantibodies against mitofusin 1 and C1qBP were elevated in a cohort of patients with SLE266.”

What the sources say

• Supported

  The Figure 3 caption (pp. 24–25) reports significantly higher IgG reactivity against both C1qBP and mitofusin 1 in patients with SLE than in healthy controls. It identifies the SLE cohort as n=87. (LLM, conf=0.94)

  cites [266] Becker, Y. L. et al. Identification of mitofusin 1 and complement component 1q subcomponent-binding protein as mitochondrial targets in systemic lupus erythematosus. Arthritis Rheumatol. https://doi.org/10.1002/art.42082 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Moreover, the in vitro transfer of healthy mitochondria to CD4+ T cells from patients with RA can restore aspartate metabolism and decrease the production of TNF, compared with untreated controls286–288.”

What the sources say

• Partly supported

  The Results sections “Mitochondrial Transfer” and “Metabolite Profiling” (page not provided) report mitochondrial transfer into mtDNA-depleted ρ0 cells and restoration of their overall metabolite profile. They do not report experiments in CD4+ T cells from patients with rheumatoid arthritis, restoration of aspartate metabolism, or decreased TNF production; searches for those terms found no supporting passage. (LLM, conf=0.83)

  cites [286] Wu, T. H. et al. Mitochondrial transfer by photothermal nanoblade restores metabolite profile in mammalian cells. Cell Metab. 23, 921–929 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [287] Rogers, R. S. & Bhattacharya, J. When cells become organelle donors. Physiology 28, 414–422 (2013). source
• Supported

  The Results section, “Mitochondria-derived aspartate controls ER size,” states that transferring healthy mitochondria into RA T cells restored aspartate generation. The Results section, “T cells rich in rough ER are TNF superproducers,” reports that transferring intact mitochondria into patients’ T cells repaired excessive TNF secretion. The Methods describe an in vitro transfer into RA CD4+ T cells with a cell/PBS control. (LLM, conf=0.94)

  cites [288] Wu, B. et al. Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation. Nat. Immunol. 22, 1551–1562 (2021). source

In the paper

“Cells with mitochondrial defects might release the damaged mitochondria to be picked up by other cells, thereby facilitating their degradation by recipient cells279.”

What the sources say

• Partly supported

  The Significance section and Discussion report that retinal ganglion cell axons shed mitochondria that adjoining astrocytes take up and degrade. The study describes otherwise healthy axons in wild-type mice; it does not establish that the releasing cells had mitochondrial defects or that the shed mitochondria were damaged. (LLM, conf=0.88)

  cites [279] Davis, C. H. et al. Transcellular degradation of axonal mitochondria. Proc. Natl Acad. Sci. USA 111, 9633–9638 (2014). sourceExperimental — accuracy not yet measured

In the paper

“investigations of mtDNA SNPs and haplogroups in SLE and RA suggest the potential utility of mtDNA alterations as early markers of diagnosis, disease activity and progression”

In the paper

“in ankylosing spondylitis, deposits of calcium hydroxyapatite are often found in close proximity to mitochondria, suggesting that calcium regulation by the organelle might be involved in the disease50”

What the sources say

• ?Not checked — no full text of the sourcecites [50] Sampson, H. W., Davis, R. W. & Dufner, D. C. Spondyloarthropathy in progressive ankylosis mice: ultrastructural features of the intervertebral disk. Acta Anat. 141, 36–41 (1991). source

In the paper

“MtDNA SNP data analysis has revealed enrichment of variants in the D-loop region and MT-ATP6 in RA”

What the sources say

• ?Not checked — no full text of the sourcecites [45] Jaiswal, K. S. et al. Differential mitochondrial genome in patients with rheumatoid arthritis. Autoimmunity 54, 1–12 (2021). source
• ?Not checked — no full text of the sourcecites [46] Du, J. et al. Germline and somatic mtDNA mutation spectrum of rheumatoid arthritis patients in the Taizhou area, China. Rheumatology 59, 2982–2991 (2020). source

In the paper

“Advancements made since the 2010s, which are reviewed herein, point to a role for the mitochondria in rheumatic diseases”

In the paper

“ex vivo studies indicate that mtROS can inhibit neutrophil apoptosis through the NF-ĸB pathway58”

What the sources say

• ?Not checked — no full text of the sourcecites [58] Vorobjeva, N. et al. Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro. Eur. J. Cell Biol. 96, 254–265 (2017). source

In the paper

“MT-ATP6 variant enrichment is mainly driven by m.8830 C > A, m.8833 G > C and m.8843 T > A SNPs that are predicted to be pathogenic46”

What the sources say

• ?Not checked — no full text of the sourcecites [46] Du, J. et al. Germline and somatic mtDNA mutation spectrum of rheumatoid arthritis patients in the Taizhou area, China. Rheumatology 59, 2982–2991 (2020). source

In the paper

“Following the release of intact mitochondria or mitochondrial components into the cytosol or the extracellular space, the bacteria-like molecular motifs of mitochondria can elicit pro-inflammatory responses by the innate immune system”

In the paper

“mitochondria can also sense and store calcium released from the endoplasmic reticulum, thus regulating its availability48,49”

What the sources say

• ?Not checked — no full text of the sourcecites [48] Kirichok, Y., Krapivinsky, G. & Clapham, D. E. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427, 360–364 (2004). source
• ?Not checked — no full text of the sourcecites [49] Rizzuto, R. et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280, 1763–1766 (1998). source

In the paper

“the variant at the 513 position of D-loop hypervariable region III is enriched in patients with RA compared with healthy individuals45”

What the sources say

• ?Not checked — no full text of the sourcecites [45] Jaiswal, K. S. et al. Differential mitochondrial genome in patients with rheumatoid arthritis. Autoimmunity 54, 1–12 (2021). source

In the paper

“dysregulation of mitochondria possibly contributes to the pathophysiology of several autoimmune diseases”

In the paper

“Data from in vivo studies indicate that this increased oxidative stress leads to exhaustion of the antioxidant capacity of the T cells34”

What the sources say

• ?Not checked — no full text of the sourcecites [34] Gergely, P. Jr et al. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Arthritis Rheum. 46, 175–190 (2002). source

In the paper

“in NZB/W F1 mice (a spontaneous model of SLE) fed a cholesterol-rich diet, supplementation with taurine inhibited mitochondrial-dependent apoptosis89”

What the sources say

• ?Not checked — no full text of the sourcecites [89] Hsu, T. C. et al. Treatment with taurine attenuates hepatic apoptosis in NZB/W F1 mice fed with a high-cholesterol diet. J. Agric. Food Chem. 56, 9685–9691 (2008). source

In the paper

“The classical pathway of complement, and particularly C1q, is thought to have protective functions in SLE pathogenesis via the ‘waste disposal hypothesis’, given the role of C1q in clearing apoptotic debris77,78”

What the sources say

• ?Not checked — no full text of the sourcecites [77] Manderson, A. P., Botto, M. & Walport, M. J. The role of complement in the development of systemic lupus erythematosus. Annu. Rev. Immunol. 22, 431–456 (2004). source
• ?Not checked — no full text of the sourcecites [78] Walport, M. J. Lupus, DNase and defective disposal of cellular debris. Nat. Genet. 25, 135–136 (2000). source

In the paper

“The potential bacterial origin of mitochondria might provide features that are recognized by the innate immune system following the release of intact organelles or fragmented mitochondrial components into the extracellular milieu.”

In the paper

“Mitochondria can exchange molecules with other organelles within the cell by generating mitochondria-derived vesicles in the cytosol, a process under the control of PINK1 (REF.151).”

What the sources say

• ?Not checked — no full text of the sourcecites [151] McLelland, G. L., Soubannier, V., Chen, C. X., McBride, H. M. & Fon, E. A. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 33, 282–295 (2014). source

In the paper

“Dysregulation of mitochondrial-dependent programmed cell death might thus contribute to inflammation in autoimmune and rheumatic conditions”

In the paper

“suggesting that different mitochondrial stressors engage unique nucleic acid sensors driven by the availability of the mitochondrial-derived nuclear component.”

In the paper

“Overall, these studies suggest that dysregulated mitochondrial dynamics has a role in rheumatic diseases”

In the paper

“Thus, with its roles in mitochondrial integrity and functions, cardiolipin might also contribute to rheumatic diseases independently of its antigenicity.”

In the paper

“Intra-articular injection of cytochrome c induces NF-ĸB-mediated arthritis in mice208.”

What the sources say

• ?Not checked — no full text of the sourcecites [208] Pullerits, R., Bokarewa, M., Jonsson, I. M., Verdrengh, M. & Tarkowski, A. Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. Rheumatology 44, 32–39 (2005). source

In the paper

“Furthermore, extracellular ATP can activate CD8+ T cells from patients with RA following ex vivo co-incubation201.”

What the sources say

• ?Not checked — no full text of the sourcecites [201] Tripathy, A., Padhan, P., Swain, N., Raghav, S. K. & Gupta, B. Increased extracellular ATP in plasma of rheumatoid arthritis patients activates CD8+ T cells. Arch. Med. Res. 52, 423–433 (2021). source

In the paper

“ATP concentrations are highly compartmentalized, with approximately a thousand-fold difference between the nanomolar concentrations found in the extracellular space and the micromolar concentrations found in the cytosol.”

In the paper

“Interestingly, the circulating autoantibody repertoire in patients with SLE includes IgG antibodies that target cytochrome c209.”

What the sources say

• ?Not checked — no full text of the sourcecites [209] Mamula, M. J., Jemmerson, R. & Hardin, J. A. The specificity of human anti-cytochrome c autoantibodies that arise in autoimmune disease. J. Immunol. 144, 1835–1840 (1990). source

In the paper

“For example, the levels of circulating ATP are increased in patients with RA compared with healthy individuals.”

In the paper

“Consistent with the release of mitochondrial components during cell death (FIG. 5), circulating levels of cytochrome c are present in inflammatory conditions such as arthritis, psoriasis or SLE205.”

What the sources say

• ?Not checked — no full text of the sourcecites [205] Adachi, N. et al. Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome. Clin. Chim. Acta 342, 127–136 (2004). source

In the paper

“Finally, fibroblasts contribute to skin fibrosis in systemic sclerosis through P2Y-mediated inflammation204.”

What the sources say

• ?Not checked — no full text of the sourcecites [204] Perera, L. M. B. et al. The regulation of skin fibrosis in systemic sclerosis by extracellular ATP via P2Y2 purinergic receptor. J. Invest. Dermatol. 139, 890–899 (2019). source

In the paper

“Non-covalent interactions between cardiolipin and various proteins are necessary for various mitochondrial functions such as energy supply.”

In the paper

“AMA-M5 are complement-fixing autoantibodies that target unknown mitochondrial antigens.”