The role of mitochondria in rheumatic diseases

In the paper

“Moreover, patients with higher disease activity have notably higher numbers of extracellular vesicle-containing immune complexes with exposed mitochondrial outer membrane markers, TOMM-20 and hexokinase I218, than patients with lower disease activity, suggesting that proteins of mitochondrial origin could be potential autoantigens in SLE217.”

What the sources say

• Disputed

  Split into 2 atoms — 0 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  cites [217] Mobarrez, F. et al. Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations. Sci. Rep. 6, 36025 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [218] Mobarrez, F. et al. Microparticles in the blood of patients with SLE: size, content of mitochondria and role in circulating immune complexes. J. Autoimmun. 102, 142–149 (2019). source

In the paper

“these mtROS also contribute to oxidative stress through the oxidation of surrounding biomolecules, eventually culminating in uncontrolled inflammation, production of neoantigens, DNA damage and DNA mutations60–63”

What the sources say

• Partly supported

  The Introduction (page not provided) says that excess ROS can lead to oxidative stress and reports lipid peroxidation associated with mitochondrial ROS. It does not link mitochondrial ROS to uncontrolled inflammation, neoantigen production, DNA damage, or DNA mutations. (LLM, conf=0.85)

  cites [60] Wang, Z. et al. The role of mitochondria-derived reactive oxygen species in hyperthermia-induced platelet apoptosis. PLoS One 8, e75044 (2013). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [61] Angelova, P. R. & Abramov, A. Y. Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett. 592, 692–702 (2018). source
• Partly supported

  The Results report that increased mitochondrial ROS in TRAPS cells lead to an antioxidant response associated with chronic oxidative stress. The Discussion says this stress may contribute to dysregulated inflammation. The paper does not establish the claimed oxidation of surrounding biomolecules, neoantigen production, DNA damage, or DNA mutations. (LLM, conf=0.87)

  cites [62] Bulua, A. C. et al. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J. Exp. Med. 208, 519–533 (2011). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [63] Tuominen, A. et al. A natural antibody to oxidized cardiolipin binds to oxidized low-density lipoprotein, apoptotic cells, and atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 26, 2096–2102 (2006). source

In the paper

“the joints of patients with RA have a higher frequency of mtDNA mutations, in addition to increased levels of synovial oxidative stress, inflammation and hypoxia, compared with the joints of healthy individuals41–43”

What the sources say

• Partly supported

  The Introduction reports increased mtDNA mutation frequency in RA joints and links it to oxidative stress and proinflammatory activity. The Introduction and Discussion also describe a hypoxic, inflamed synovial environment. However, these passages do not establish that all four features are increased relative to joints of healthy individuals; the reported comparisons concern other conditions or variation within inflammatory arthritis. (LLM, conf=0.86)

  cites [41] Biniecka, M. et al. Dysregulated bioenergetics: a key regulator of joint inflammation. Ann. Rheum. Dis. 75, 2192–2200 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [42] Biniecka, M. et al. Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis. Arthritis Rheum. 63, 2172–2182 (2011). source
• ?Not checked — no full text of the sourcecites [43] Harty, L. C. et al. Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis. Ann. Rheum. Dis. 71, 582–588 (2012). source

In the paper

“mitochondrial reactive oxygen species (mtROS)56, known to contribute to inflammatory responses and antimicrobial activities57–59”

What the sources say

• Partly supported

  The Results section ('RNP IC-mediated NETosis is dependent on mitochondrial ROS') links mitochondrial ROS to neutrophil extracellular trap formation, and the Discussion links it to autoimmune inflammation. The passages do not establish that mitochondrial ROS contribute to antimicrobial activity; the paper’s mention of pathogen-induced traps does not make that specific connection. (LLM, conf=0.85)

  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
• ?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
• ?Not checked — no full text of the sourcecites [59] Rousset, S. et al. The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine 35, 135–142 (2006). source

In the paper

“MtROS are implicated in neutrophil degranulation, neutrophil extracellular trap (NET) formation57 and the production of cytokines59”

What the sources say

• Supported

  The citation is attached to NET formation, not to the separately cited cytokine-production claim. The Discussion reports that mitochondrial ROS can drive NETosis after RNP immune-complex stimulation and in the studied lupus and CGD neutrophil subsets. (LLM, conf=0.93)

  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
• ?Not checked — no full text of the sourcecites [59] Rousset, S. et al. The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine 35, 135–142 (2006). source

In the paper

“MtDNA is inherited maternally26,27, with little evidence of biparental recombination at the population level28”

What the sources say

• ?Not checked — no full text of the sourcecites [26] Giles, R. E., Blanc, H., Cann, H. M. & Wallace, D. C. Maternal inheritance of human mitochondrial DNA. Proc. Natl Acad. Sci. USA 77, 6715–6719 (1980). source
• Supported

  The Abstract describes maternal inheritance as the accepted pattern and reports no evidence of paternal mtDNA transmission in the offspring studied. The Introduction says population-level signals proposed as evidence of paternal–maternal recombination can instead be explained by homoplasy, supporting the cautious wording that evidence for such recombination is limited. The paper does not itself test recombination in a population sample. (LLM, conf=0.87)

  cites [27] Pyle, A. et al. Extreme-depth re-sequencing of mitochondrial DNA finds no evidence of paternal transmission in humans. PLoS Genet. 11, e1005040 (2015). source
• ?Not checked — no full text of the sourcecites [28] Elson, J. L. et al. Analysis of European mtDNAs for recombination. Am. J. Hum. Genet. 68, 145–153 (2001). source

In the paper

“Mitochondria are thought to derive from a bacterial ancestor10,11 (according to the endosymbiotic hypothesis)”

What the sources say

• Supported

  The Abstract says mitochondria may be derived from α-proteobacteria and describes an endosymbiotic scenario leading to modern mitochondria. It also identifies Rickettsia as a possible model for the bacterial ancestor. Page numbers are not provided in the supplied copy. (LLM, conf=0.94)

  cites [10] Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140 (1998). source
• ?Not checked — no full text of the sourcecites [11] Gray, M. W. Mitochondrial evolution. Cold Spring Harb. Perspect. Biol. 4, a011403 (2012). source

In the paper

“The causes of these diseases are largely unknown but are thought to involve various factors, including genetic predispositions, environmental factors, dysfunctions of the immune system, altered cell death, reactive oxygen species (ROS) and overproduction of self-reactive antibodies1,2”

What the sources say

• Partly supported

  The Introduction (p. 4) describes immune dysfunction and autoantibody formation in systemic lupus erythematosus (SLE). The oxidative-stress section (pp. 10–11) discusses environmental factors, ROS, abnormal apoptosis and resulting autoantibody formation. The paper addresses SLE rather than rheumatic diseases generally, and these passages do not establish the broader claim that their causes are largely unknown or identify genetic predisposition as a factor. (LLM, conf=0.87)

  cites [1] Wincup, C. & Radziszewska, A. Abnormal mitochondrial physiology in the pathogenesis of systemic lupus erythematosus. Rheum. Dis. Clin. North. Am. 47, 427–439 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and the sections on dying-cell clearance and modified autoantigens describe genetic susceptibility, immune activation, altered cell death, oxidative changes, and autoantibodies in systemic lupus erymatosus (page numbers unavailable). The paper does not establish this full list—including environmental factors and reactive oxygen species—as causes of rheumatic diseases generally, nor does it state that their causes are largely unknown. (LLM, conf=0.84)

  cites [2] Colonna, L., Lood, C. & Elkon, K. B. Beyond apoptosis in lupus. Curr. Opin. Rheumatol. 26, 459–466 (2014). sourceExperimental — accuracy not yet measured

In the paper

“The mitochondrion regulates various biological pathways (for example, cellular energy production, apoptosis, calcium regulation and thermogenesis)”

What the sources say

• ?Not checked — no full text of the sourcecites [4] Miller, W. L. Role of mitochondria in steroidogenesis. Endocr. Dev. 20, 1–19 (2011). source
• ?Not checked — no full text of the sourcecites [5] Miller, W. L. & Portale, A. A. Genetics of vitamin D biosynthesis and its disorders. Best. Pract. Res. Clin. Endocrinol. Metab. 15, 95–109 (2001). source
• Partly supported

  The section ‘The (Mitochondrial) Heme Synthesis Metabolon’ (page unavailable) discusses mitochondrial carbon flux and its interplay with the TCA cycle, while the References (page unavailable) include studies linking mitochondrial membrane changes to apoptosis. These provide limited support for metabolic and apoptotic roles, but the paper does not state the broader claim about energy production or address calcium regulation or thermogenesis. (LLM, conf=0.72)

  cites [6] Piel, R. B. III, Dailey, H. A. Jr & Medlock, A. E. The mitochondrial heme metabolon: insights into the complex(ity) of heme synthesis and distribution. Mol. Genet. Metab. 128, 198–203 (2019). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [7] Schlame, M. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes. J. Lipid Res. 49, 1607–1620 (2008). source

In the paper

“Mitochondrial ROS can oxidize mitochondrial nucleic acids, causing the expression of aberrant proteins, and/or directly induce post-translational oxidation of local proteins, lipid peroxidation and oxidative damage to nuclear DNA and/or mtDNA60,66,67”

What the sources say

• Partly supported

  The Results section (page unavailable) reports lipid and cardiolipin peroxidation in hyperthermia-treated platelets and links both to mitochondrial ROS. The passages do not support the additional claims about oxidation of mitochondrial nucleic acids, aberrant protein expression, post-translational protein oxidation, or oxidative damage to nuclear DNA or mtDNA. (LLM, conf=0.88)

  cites [60] Wang, Z. et al. The role of mitochondria-derived reactive oxygen species in hyperthermia-induced platelet apoptosis. PLoS One 8, e75044 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  The “Mitochondria and electron transfer” section says mitochondria generate ROS, and “Chemical targets and reactions mediated by ROS” says ROS can modify proteins, lipids, DNA and RNA. The copy does not specifically link mitochondrial ROS to aberrant protein expression, lipid peroxidation, or damage to nuclear versus mitochondrial DNA. No page numbers are provided in the indexed passages. (LLM, conf=0.85)

  cites [66] Dickinson, B. C. & Chang, C. J. Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat. Chem. Biol. 7, 504–511 (2011). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [67] Morgan, P. E., Sturgess, A. D. & Davies, M. J. Evidence for chronically elevated serum protein oxidation in systemic lupus erythematosus patients. Free Radic. Res. 43, 117–127 (2009). source

In the paper

“exposure of isolated healthy T cells to type I interferon leads to impaired mitochondrial respiration74, pointing to a role for type I interferon in mediating mitochondrial metabolic defects”

What the sources say

• Partly supported

  The Results section (“TCR and IFN signalling together induce CD8+ T cell metabolic rewiring”; page unavailable) reports reduced spare respiratory capacity after seven days of IFNα exposure in healthy-donor CD8+ T cells, with or without T-cell activation. The Results section on NAD+ consumption says defective mitochondrial respiration occurred in TCR-stimulated CD8+ T cells upon restimulation. The claim captures a role for type I interferon but omits those cell-type and experimental-condition qualifiers. (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

“An increase in spare respiratory capacity in CD8+ T cells is a marker of longevity, suggesting that C1q regulates the viability and turnover of memory precursor effector”

What the sources say

• Partly supported

  The passages on MPECs (page not provided) report impaired spare respiratory capacity in C1q-deficient cells, alongside faster turnover and findings suggesting that C1q influences their viability. Our copy says spare respiratory capacity correlates with mitochondrial mass, but does not identify increased capacity as a marker of CD8+ T-cell longevity. (LLM, conf=0.85)

  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

“Dietary supplementation with N-acetylcysteine (a precursor of glutathione) inhibits the mTOR pathway, restores the mitochondrial membrane potential and increases the mitochondrial mass in lymphocytes from patients with SLE85,86”

What the sources say

• Partly supported

  The Results section reports that NAC reduced mTOR activity and increased mitochondrial mass, particularly in double-negative T cells. But it also reports that NAC increased mitochondrial hyperpolarization in lupus T cells; it does not describe this as restoring membrane potential to normal. The claim also generalizes the mitochondrial-mass finding from a T-cell subset to lymphocytes broadly. (LLM, conf=0.88)

  cites [85] Lai, Z. W. et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 64, 2937–2946 (2012). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page not available in our copy) says NAC blocked mTOR activation in SLE patients, but explicitly says it failed to moderate mitochondrial hyperpolarization, contrary to the claimed restoration of membrane potential. The retrieved passages do not report an increase in mitochondrial mass. (LLM, conf=0.90)

  cites [86] Perl, A. et al. Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin. Metabolomics 11, 1157–1174 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Accumulation of succinate in TH10 cells enables an altered type of electron transport chain activity, ultimately leading to the production of IL-10 and mtROS, and acquisition of B cell helper functions75”

What the sources say

• Partly supported

  The Abstract reports succinate-fueled reverse electron transport as the cause of mtROS accumulation in the lupus CD4+ T-cell population, and says the cells provide B-cell help through IL-10 and succinate. It does not establish that reverse electron transport leads to IL-10 production; the claim folds that separate finding into the same causal chain. (LLM, conf=0.84)

  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

In the paper

“The production of ROS and oxidized proteins is increased in mesenchymal stem cells incubated with sera from patients with ankylosing spondylarthritis compared with cells incubated with healthy sera. This finding suggests that circulating factors mediate mitochondrial oxidative stress in the pathophysiology of the disease64”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [64] Ye, G. et al. Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis. Cell Death Dis. 11, 775 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Together, these elements suggest that C1q regulates mitochondrial activity in memory precursor effector cells and that an impairment of this regulation leads to an expansion of autoreactive and pro-inflammatory short-lived effector cells and the suppression of protective memory precursor effector cells81,83”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [83] Weyand, C. M. & Goronzy, J. J. A mitochondrial checkpoint in autoimmune disease. Cell Metab. 28, 185–186 (2018). source

In the paper

“C1q-deficient mice have increased numbers of short-lived effector cells and decreased numbers of memory precursor effector cells compared with their wild type littermates, suggesting that C1q promotes the survival of short-lived effector cells”

What the sources say

• Partly supported

  The passage describing the cGvHD model (indexed as Abstract; page unavailable) reports a relative expansion of short-lived effector cells and a corresponding reduction in memory precursor effector cells in C1q-deficient mice, but gives proportions rather than the absolute numbers claimed. A later passage says C1q controls the survival of memory precursor effector cells, not short-lived effector cells. (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). sourceExperimental — accuracy not yet measured

In the paper

“Variants of the gene encoding the small GTPase RAB4A (also known as HRES-1/RAB4) are associated with SLE and its expression is increased in CD4+ T cells from patients with SLE116”

What the sources say

• Partly supported

  The Introduction states that polymorphic alleles of the HRES-1 locus are associated with SLE and that HRES-1/Rab4 is overexpressed in T cells of patients with SLE. It does not establish that the increased expression is specifically in CD4+ T cells; the Discussion’s reference to naïve CD4 T cells concerns mice. (LLM, conf=0.85)

  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

“The mitochondrial spare respiratory capacity and mitochondrial biogenesis were impaired in C1q-deficient memory precursor effector cells”

What the sources say

• Supported

  The passage indexed under Abstract reports impaired mitochondrial spare respiratory capacity and reduced mitochondrial content in C1qa−/− memory precursor effector cells compared with wild-type cells. It also describes a C1q-dependent pathway regulating their mitochondrial biogenesis, consistent with the claim. (LLM, conf=0.92)

  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

“The mitochondrial mass is dynamic; individual organelles can fuse or shed from the network to address the metabolic requirements of the cell97–99”

What the sources say

• Supported

  The Introduction describes continuous transitions between connected and separated mitochondria through fusion and fission, and links remodeling of mitochondrial architecture to bioenergetic adaptation. Section 4(a) describes individual mitochondria reconnecting with the network or remaining separate and being removed. The paper supports the claim’s account of a changing mitochondrial network responding to metabolic needs. (LLM, conf=0.87)

  cites [97] Liesa, M. & Shirihai, O. S. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 17, 491–506 (2013). source
• Partly supported

  The Results and Discussion report that β-cell mitochondria repeatedly fuse and undergo fission, changing how they are connected in a network. The paper links these dynamics to responses to high nutrient exposure, but does not establish that total mitochondrial mass changes or that organelles join and leave the network to meet the cell’s metabolic requirements generally. Page numbers were not available in our copy. (LLM, conf=0.84)

  cites [98] Molina, A. J. et al. Mitochondrial networking protects β-cells from nutrient-induced apoptosis. Diabetes 58, 2303–2315 (2009). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) describes dynamic mitochondrial networks shaped by fusion and fission, and the Results and discussion directly document fusion of individual mitochondria. The paper does not establish that these changes occur to meet the cell’s metabolic requirements, nor does it measure mitochondrial mass. (LLM, conf=0.85)

  cites [99] Karbowski, M. et al. Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. J. Cell Biol. 164, 493–499 (2004). sourceExperimental — accuracy not yet measured

In the paper

“The presence of N-formylated peptides and cardiolipin in mitochondria, and the genetic similarity of the genomes of the mitochondrion and Rickettsia prowazekii (a pathogen responsible for epidemic typhus) suggest that mitochondria originate from a symbiotic relationship (endosymbiosis) between an α-proteobacterium and a primitive eukaryotic cell10.”

What the sources say

• Partly supported

  The Abstract and ‘Mitochondrial affinities’ section (pages not provided) support an α-proteobacterial endosymbiotic origin and a close genetic relationship between mitochondria and R. prowazekii. Our copy does not identify mitochondrial N-formylated peptides or cardiolipin as evidence for that origin; searches for those terms found no such passage. (LLM, conf=0.88)

  cites [10] Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140 (1998). sourceExperimental — accuracy not yet measured

In the paper

“treatment with VBIT-4, a VDAC oligomerization inhibitor, can abrogate the SLE-like symptoms of lupus-prone mice, which is paralleled by a concomitant decrease in cytosolic mtDNA”

What the sources say

• Supported

  The passages indexed under Abstract report that VBIT-4 blocked skin lesions and reduced multiple other lupus-like disease measures in MpJ-Faslpr mice. They also state that VBIT-4 abrogated the elevated cytosolic mtDNA in splenocytes from those mice. No page numbers are provided in our copy. (LLM, conf=0.93)

  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). source

In the paper

“Cytosolic release of mtDNA can occur in live cells (as opposed to apoptotic cells) via pores formed by VDAC oligomers independent of BAX–BAK macropores and can activate the cGAS–STING pathway, as shown in mouse embryo fibroblasts deficient in Endog (a nuclear DNA-encoded mitochondrial endonuclease)148”

What the sources say

• Supported

  The Abstract (page unavailable) states that oxidatively stressed mitochondria release short mtDNA fragments through VDAC oligomer pores in live cells. The passages on Endog-deficient mouse embryo fibroblasts report BAX/BAK-independent mtDNA release without cellular apoptosis and activation of cGAS–STING by cytosolic mtDNA. (LLM, conf=0.94)

  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). source

In the paper

“supplementation with an NAD+ precursor, nicotinamide mononucleotide, can reverse the SLE-like metabolic features of CD8+ T cells and improve their viability74”

What the sources say

• Supported

  The Results section states that NMN rectified the metabolic changes caused by prolonged IFNα exposure and improved CD8+ T-cell viability. It identifies those experimental conditions as mimicking abnormalities observed in CD8+ T cells from IFN-High SLE patients, so “SLE-like” accurately describes the finding. (LLM, conf=0.94)

  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

“This finding contrasts with previous work showing that mtDNA stress, induced by the haploinsufficiency of the mitochondrial transcription factor A (TFAM), can lead to robust cGAS–STING activation147”

What the sources say

• Supported

  The paper reports that Tfam+/− cells show mtDNA stress and that cGAS knockdown or STING loss largely abrogates the resulting interferon-stimulated gene expression. Extended Data Figure 8 explicitly describes TFAM depletion as triggering mtDNA release that activates cGAS and STING. (LLM, conf=0.93)

  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

“Circulating mtDNA, which can stimulate TLR9 signalling, is present in various inflammatory conditions, including RA152,153, SLE154, Sjögren syndrome155, cancers156,157, neurodegenerative diseases158–161, cardiovascular disease162, type 2 diabetes163,164, HIV165, liver injuries166, traumas167, corrosive injuries168, sepsis169, ageing170 and stress171,172.”

What the sources say

• Supported

  The citation is attached to RA, not to the other conditions, which have separate citations. The sections “Comparison of cfDNA Observations Between SLE and RA” and “Based on Intracellular Origin” report mtDNA in RA patients and explain that mtDNA can activate TLR9, respectively. Page numbers are not available in the supplied passages. (LLM, conf=0.91)

  cites [152] Duvvuri, B. & Lood, C. Cell-Free DNA as a biomarker in autoimmune rheumatic diseases. Front. Immunol. 10, 502 (2019). source
• Supported

  The citation is attached to RA in the list, so the other conditions are not attributed to this paper. The Discussion reports extracellular mtDNA in plasma samples from patients with RA and says patients with elevated joint mtDNA tended to have free mtDNA in their bloodstream. (LLM, conf=0.92)

  cites [153] Hajizadeh, S., DeGroot, J., TeKoppele, J. M., Tarkowski, A. & Collins, L. V. Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis. Arthritis Res. Ther. 5, R234–R240 (2003). source
• ?Not checked — no full text of the sourcecites [154] Wang, H., Li, T., Chen, S., Gu, Y. & Ye, S. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin. Arthritis Rheumatol. 67, 3190–3200 (2015). source
• ?Not checked — no full text of the sourcecites [155] Barrera, M.-J. et al. Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: potential role in Sjögren’s syndrome. Autoimmun. Rev. 20, 102867 (2021). source

In the paper

“These CD8+ T cells have various mitochondrial defects such as an increased mitochondrial mass, mitochondrial hyperpolarization and impaired mitochondrial bioenergetics, including a reduced spare respiratory capacity”

What the sources say

• Supported

  The Results section on aberrant mitochondria reports increased mitochondrial size and membrane hyperpolarization in CD8+ T cells from IFN-High SLE patients. The Results section on respiratory capacity reports significantly reduced spare respiratory capacity and concludes that these larger, hyperpolarized mitochondria were bioenergetically impaired. No page numbers are provided in our copy. (LLM, conf=0.91)

  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

“Extracellular mtRNA might thus function as a ligand for TLR7 and TLR8 (REFS.173,174) and contribute to SLE.”

What the sources say

• Partly supported

  The Introduction (page unavailable) says human TLR8 senses mitochondrial rRNA, and the Results and Discussion report that a mitochondrial RNA-derived fragment activated murine cells through TLR7. But the paper does not establish that extracellular mtRNA activates both receptors or contributes to SLE; it says whether its findings extend to autoimmunity remains to be evaluated. (LLM, conf=0.88)

  cites [173] Kruger, A. et al. Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA. EMBO Rep. 16, 1656–1663 (2015). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction says TLR7 senses viral single-stranded RNA, and the Discussion describes a mitochondrial protein that regulates TLR7 signaling. Neither passage addresses extracellular mitochondrial RNA as a ligand for TLR7 or TLR8, or a contribution to SLE. Searches for extracellular mtRNA and SLE found no passage making those points. (LLM, conf=0.76)

  cites [174] Shi, H. X. et al. Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action. PLoS Pathog. 7, e1002057 (2011). sourceExperimental — accuracy not yet measured

In the paper

“The mtDSBs lead to herniation of the inner mitochondrial membrane owing to the formation of pores composed of the pro-apoptotic proteins BAX and BAK, suggesting the involvement of these pores in mtRNA leakage.”

What the sources say

• Supported

  The main text (page not provided) says the authors’ data are consistent with mitochondrial herniation through BAK–BAX macro-pores after mtDNA damage. It also states that mtDNA breaks trigger BAK–BAX-mediated herniation, releasing mitochondrial RNA into the cytoplasm. The paper presents herniation as a supported model rather than a directly established mechanism, which is consistent with the citing sentence’s qualified wording. (LLM, conf=0.91)

  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

“a study published in 2021 revealed that a proportion of erythrocytes contain mitochondria in SLE119”

What the sources say

• Supported

  The Results section (“RBCs from patients with active SLE retain mitochondria”) reports mitochondria in up to 37.2% of mature RBCs in a fraction of patients with SLE. The same passage states that mitochondria are normally completely removed during maturation into RBCs. (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

“splenocytes from lupus-prone mice have more VDAC pores and cytosolic mtDNA than splenocytes from wild-type mice”

What the sources say

• Supported

  The passage labelled Abstract reports that splenocytes from MpJ-Faslpr lupus-prone mice had more VDAC1 oligomers and elevated cytosolic mtDNA than splenocytes from MpJ control mice. The paper also identifies VDAC oligomers as forming mitochondrial pores, supporting the claim’s use of “VDAC pores.” (LLM, conf=0.94)

  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). source

In the paper

“within the mitochondrion, mtDNA is transcribed into polycistronic RNAs and then processed into mature mtRNA22,23.”

What the sources say

• Supported

  The Introduction states that mtDNA produces long polycistronic precursor transcripts that are processed to release individual RNAs, which then undergo maturation. The Results section on mitochondrial gene expression likewise describes precursor transcripts being processed into individual mRNAs. No page numbers are provided in our copy. (LLM, conf=0.94)

  cites [22] Mercer, T. R. et al. The human mitochondrial transcriptome. Cell 146, 645–658 (2011). source
• ?Not checked — no full text of the sourcecites [23] Rorbach, J. & Minczuk, M. The post-transcriptional life of mammalian mitochondrial RNA. Biochem. J. 444, 357–373 (2012). source

In the paper

“although mtDNA transcription points towards the production of single-stranded mtRNA, some evidence supports the existence of unstable double-stranded mtRNA during homeostasis150.”

What the sources say

• Supported

  The paper reports a highly unstable native mitochondrial double-stranded RNA species in cells. It also reports rapid turnover of this RNA under control conditions, supporting its existence despite suppression of its steady-state levels (Abstract; page not specified). (LLM, conf=0.94)

  cites [150] Dhir, A. et al. Mitochondrial double-stranded RNA triggers antiviral signalling in humans. Nature 560, 238–242 (2018). source

In the paper

“Mitochondria from CD8+ T cells of patients with SLE and a high interferon-stimulated gene signature are morphologically distinct from those of patients who do not have this gene signature, with the increased mitochondrial mass hindering mitochondrial metabolism in these cells74”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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

“defective degradation leads to double-stranded mtRNA accumulation in the organelle, subsequent cytosolic leakage of double-stranded mtRNA and type I interferon production150.”

What the sources say

• Partly supported

  The paper reports that loss of either mitochondrial RNA degradosome component causes double-stranded mtRNA accumulation. However, its discussion of dsRNA localization and IFNB1 induction distinguishes the two: PNPase depletion permits cytosolic release and a type I interferon response, whereas SUV3 depletion leaves the RNA restricted to mitochondria without that response. The claim is therefore too broad if 'defective degradation' includes both defects. (LLM, conf=0.88)

  cites [150] Dhir, A. et al. Mitochondrial double-stranded RNA triggers antiviral signalling in humans. Nature 560, 238–242 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Unlike other cell types, human neutrophils do not undergo mitophagy following mitochondrial damage but instead release mtDNA–TFAM complexes175.”

What the sources say

• Supported

  The Results section, “Extrusion of mtDNA–protein complexes as a neutrophil alternative to mitophagy” (page unavailable), reports that neutrophils have impaired autophagosome–lysosome fusion after mitochondrial depolarization and increased mtDNA extrusion. The Results section on extruded neutrophil complexes identifies TFAM as the carrier of the released mtDNA. (LLM, conf=0.88)

  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

“overexpression of RAB4A in various models is associated with defective mitophagy, increased mitochondrial mass, the production of antinuclear autoantibodies and nephritis116,118”

What the sources say

• Supported

  The Results sections report that HRES-1/Rab4 overexpression inhibited mitophagy and increased mitochondrial mass in human cells. They also report Rab4A overexpression and mitochondrial accumulation in lupus-prone mice, with ANA production and nephritis developing later; the claim describes an association, not direct causation. (LLM, conf=0.90)

  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). source
• ?Not checked — no full text of the sourcecites [118] Hoppins, S., Lackner, L. & Nunnari, J. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76, 751–780 (2007). source

In the paper

“Moreover, pDCs activated by oxidized mtDNA induce a unique population of CD4+ T cells, TH10 (CXCR5−CXCR3+PD1hiCD4+ T cell), that have altered metabolic features; these cells have accumulated levels of mtROS and succinate and produce large amounts of IL-10 and IFNγ but not IL-21 (REF.75).”

What the sources say

• Supported

  In the copy’s Abstract-labelled passages, the authors describe CD4+ T cells generated with oxidized-mtDNA-activated pDCs that produce high IFNγ and IL-10. The same passages report increased mitochondrial ROS and succinate, identify CXCR5−CXCR3+PD1hi cells, and state that these cells do not express IL-21. No page numbers are supplied in the copy. (LLM, conf=0.90)

  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

“CD8+ T cells from patients with a high type I interferon gene signature are more prone to spontaneous cell death than cells from both healthy individuals and patients that do not express this signature74, suggesting that impaired metabolic fitness owing to prolonged type I interferon exposure decreases the survivability of cells”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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

“chronic exposure to high doses of IFNα and TCR stimulation, a combination probably unique to patients with SLE, leads to increased consumption of NAD+ and a decreased NAD+ to NADH ratio in these cells, resulting in mitochondrial dysfunction and cell death”

What the sources say

• Supported

  The Results section (“IFNα exposure increases NAD+ consumption in CD8+ T cells”) states that prolonged IFNα exposure in TCR-stimulated CD8+ T cells increased NAD+ consumption, lowered the NAD+/NADH ratio, impaired mitochondrial respiration upon restimulation, and reduced viability. The figure caption specifies treatment with 1000 U/ml IFNα for seven days; a separate Results section also reports increased spontaneous cell death with prolonged IFNα exposure and T-cell activation. (LLM, conf=0.93)

  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

“These associations suggest that assessing fMet levels and/or mtDNA haplogroups might be utilized as biomarkers to predict certain disease manifestations186.”

What the sources say

• Supported

  The disease-risk results (pp. 8–9) link fMet levels to incident renal and cardiovascular diseases and discuss its potential as a marker of ageing-related disease. The same section (p. 8) reports that haplogroup Uk has been associated with reduced risk of ischemic stroke and Parkinson’s disease. These findings support the citing sentence’s tentative proposal, though the paper does not establish a validated prediction test. (LLM, conf=0.86)

  cites [186] Cai, N. et al. Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases. Nat. Med. 27, 1564–1575 (2021). source

In the paper

“Notably, various mtDNA variants are associated with levels of circulating fMet, and fMet levels are associated with increased risks of various diseases (for example, of the renal, pulmonary or cardiovascular systems).”

What the sources say

• Supported

  The section on common mtDNA variants (p. 4) reports associations between multiple mtDNA variants and blood fMet levels. The disease-risk section (pp. 8–9) reports positive associations between fMet levels and incident renal disease, chronic obstructive pulmonary disease, and several cardiovascular diseases. (LLM, conf=0.94)

  cites [186] Cai, N. et al. Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases. Nat. Med. 27, 1564–1575 (2021). source

In the paper

“Mitochondria are released from cells undergoing TNF-induced necroptosis via RIP1–RIP3 activation, as shown in Fas-associated protein with death domain (FADD)-deficient Jurkat T cells and L929 cells (a murine fibroblast cell line); this mitochondrial release occurs before plasma membrane disruption, suggesting that the mitochondria are actively released from necroptotic cells212.”

What the sources say

• Supported

  The Results section identifies TNF-α-treated FADD-deficient Jurkat and L929 cells as a model of necroptosis via RIP1/RIP3 activation and reports extracellular mitochondria from both cell types. In the section on mitochondrial release, loss of mitochondrial staining precedes detectable plasma membrane disruption; the authors interpret this as suggesting regulated release. (LLM, conf=0.90)

  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

“The extruded mitochondrial components contain highly oxidized mtDNA that can provoke type I interferon production in a cGAS–STING-dependent manner, a process probably well conserved among all cell types given the ubiquity of these molecules.”

What the sources say

• Partly supported

  The Results (‘RNP ICs induce oxidized mtDNA release’ and ‘NET-bound oxidized mtDNA is pro-inflammatory’; page not provided) report release of oxidized mtDNA and STING-dependent interferon-related responses. They do not establish that the response is conserved across all cell types: oxidized mtDNA stimulated PBMCs and THP1 cells but did not activate neutrophils despite being internalized. (LLM, conf=0.87)

  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 human neutrophils, the binding of FPR1 and FPR2 to N-formylated peptides triggers the release of Ca2+ into the cytosol and ultimately leads to the migration and activation of neutrophils13”

What the sources say

• Partly supported

  The paper reports that formyl peptides signal through FPR1 and FPRL-1 and that human neutrophils respond to mitochondrial DAMPs with increased intracellular calcium, activation, and migration (Abstract; page not provided). But its experiments attribute these calcium and migration responses to FPR1: blocking FPR1 inhibits them, while an FPRL-1 control antibody has no effect on the calcium response. The copy therefore does not establish the claimed role for both receptors in that response. (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

“Blocking mtDNA extrusion, using a mitochondrial ROS scavenger, ameliorates SLE-like disease in lupus-prone mice, implicating oxidized mtDNA as a pathogenic driver in SLE57”

What the sources say

• Supported

  The Results section on oxidized mtDNA release reports that inhibiting mitochondrial ROS reduced mtDNA in released NETs. The in vivo Results report that prophylactic treatment with the mitochondrial ROS scavenger MitoTEMPO reduced NETosis and lupus-like disease in lupus-prone mice; the Discussion suggests that released oxidized mtDNA may contribute to autoimmunity. (LLM, conf=0.88)

  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

“The expression of P2X is dysregulated in PBMCs from patients with SLE and in B cells obtained from a spontaneous mouse model of SLE202,203 and is thought to be associated with disease pathogenesis and progression202.”

What the sources say

• Partly supported

  The Results in the Abstract and the Discussion (pages unavailable in our copy) report reduced P2X7R expression in PBMCs from SLE patients and discuss a possible role in pathogenesis. The paper does not establish an association with disease progression. Its mouse-model discussion concerns renal tissue, not B cells from a spontaneous SLE mouse model. (LLM, conf=0.86)

  cites [202] Furini, F. et al. P2X7 receptor expression in patients with serositis related to systemic lupus erythematosus. Front. Pharmacol. 10, 435 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion (page unavailable) report reduced cell-surface P2X7 receptor expression in B220+ T cells from lupus-prone MRL/lpr mice and suggest that impaired signaling could contribute to autoimmune pathology. They do not establish dysregulated expression in mouse B cells—B220+ here denotes a T-cell population—or report measurements in PBMCs from patients with SLE. The proposed link to disease is qualified, not a demonstrated association with progression. (LLM, conf=0.88)

  cites [203] Le Gall, S. M. et al. Loss of P2X7 receptor plasma membrane expression and function in pathogenic B220+ double-negative T lymphocytes of autoimmune MRL/lpr mice. PLoS One 7, e52161 (2012). sourceExperimental — accuracy not yet measured

In the paper

“More importantly, mitochondrial fMet levels can distinguish patients based on disease activity and are associated with current joint erosion and joint space narrowing at baseline.”

What the sources say

• Partly supported

  The Results report that total fMet levels distinguished RA patients by disease activity in cohorts RA1 and RA4. They also report correlations with current joint erosion and joint space narrowing in RA2, a follow-up cohort, but do not establish those associations at baseline. The paper discusses baseline fMet levels separately when assessing later outcomes. (LLM, conf=0.86)

  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). sourceExperimental — accuracy not yet measured

In the paper

“Notably, compared with neutrophils from healthy individuals, neutrophils from patients with SLE, particularly low-density granulocytes, have high baseline levels of mitochondrial ROS generation that promotes spontaneous NET formation and the extrusion of inflammatory oxidized mtDNA57.”

What the sources say

• Supported

  The Results section ('Mitochondrial ROS drive pro-inflammatory NETosis in SLE LDGs') reports greater mitochondrial superoxide production in SLE low-density granulocytes than in healthy control neutrophils. It also reports that this superoxide is necessary for spontaneous NET formation and that the released NETs are enriched in inflammatory oxidized mtDNA. (LLM, conf=0.92)

  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

“Mitochondrial fMet levels are elevated in patients with RA compared with healthy individuals and are associated with neutrophil-mediated inflammation and disease progression, including the development of rheumatoid nodules185.”

What the sources say

• Supported

  The Introduction states this claim directly. The Results report elevated total fMet in RA cohorts versus healthy controls, associations with neutrophil activation markers, and baseline mtNFP levels predicting later rheumatoid nodules. (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

“Recognition of extracellular ATP by P2X7 elicits the release of intracellular potassium and an increase in cytosolic calcium, resulting in activation of NLRP3 and downstream release of pro-inflammatory cytokines (for example, IL-1β, IL-6 and IL-8 and MCP1)198–200.”

What the sources say

• Partly supported

  The Abstract and Discussion report that extracellular ATP activates P2X7R, causing K+ efflux and increased cytosolic Ca2+, with NLRP3-dependent IL-1β secretion. They do not establish IL-6, IL-8, or MCP1 release downstream of that pathway; the Discussion mentions IL-6 production by macrophages in a different context. (LLM, conf=0.91)

  cites [198] Karmakar, M., Katsnelson, M. A., Dubyak, G. R. & Pearlman, E. Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP. Nat. Commun. 7, 10555 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [199] Seiffert, K., Ding, W., Wagner, J. A. & Granstein, R. D. ATPγS enhances the production of inflammatory mediators by a human dermal endothelial cell line via purinergic receptor signaling. J. Invest. Dermatol. 126, 1017–1027 (2006). source
• ?Not checked — no full text of the sourcecites [200] McDonald, B. et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330, 362–366 (2010). source

In the paper

“Finally, antibodies to sarcosine dehydrogenase (AMA-M7 antibodies) have been detected in patients with heart conditions244–247.”

What the sources say

• ?Not checked — no full text of the sourcecites [244] Klein, R., Maisch, B., Kochsiek, K. & Berg, P. A. Demonstration of organ specific antibodies against heart mitochondria (anti-M7) in sera from patients with some forms of heart diseases. Clin. Exp. Immunol. 58, 283–292 (1984).
• ?Not checked — no full text of the sourcecites [245] Cicek, G., Schiltz, E., Hess, D., Staiger, J. & Brandsch, R. Analysis of mitochondrial antigens reveals inner membrane succinate dehydrogenase flavoprotein subunit as autoantigen to antibodies in anti-M7 sera. Clin. Exp. Immunol. 128, 83–87 (2002). source
• Supported

  The paper’s opening summary states that anti-M7 antibodies in sera from patients with dilated cardiomyopathy and myocarditis recognize bacterial sarcosine dehydrogenase. The Results also report anti-M7-positive sera in patients with those conditions and other heart diseases. Page numbers are not provided in the supplied passages. (LLM, conf=0.94)

  cites [246] Otto, A. et al. Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD. Clin. Exp. Immunol. 111, 541–547 (1998). source
• ?Not checked — no full text of the sourcecites [247] Stahle, I., Brizzio, C., Barile, M. & Brandsch, R. Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins, effect of vitamin B2 and epitope mapping. Clin. Exp. Immunol. 115, 404–408 (1999). source

In the paper

“Nine of these anti-mitochondrial antibodies (AMA-M1 to AMA-M9) have been identified and named according to their specific characteristics (that is, the targets, pathological context of detection, appearance by indirect immunofluorescence (IIF), band labelling by western blot and ability to bind to complement)229–231.”

What the sources say

• ?Not checked — no full text of the sourcecites [229] Berg, P. A. & Klein, R. Mitochondrial antigens and autoantibodies: from anti-M1 to anti-M9. Klin. Wochenschr. 64, 897–909 (1986). source
• Partly supported

  The Introduction identifies AMA-M1 through AMA-M9, and Table 1 lists their molecular targets, associated diseases, and detection methods, including IIF and complement fixation tests. It does not say the classes were named according to those characteristics, nor does it describe IIF appearance or western-blot band labelling as naming criteria. No page numbers are available in our copy. (LLM, conf=0.87)

  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
• Partly supported

  The Discussion describes nine AMA types, M1–M9, targeting distinct epitopes, and the Introduction’s Figure 1 caption links several types to targets and disease contexts. Neither passage says the types were named according to indirect immunofluorescence appearance, western blot band labelling, or complement binding; the copy also says some targets remain unidentified. (LLM, conf=0.87)

  cites [231] Becker, Y. et al. Autoantibodies in systemic lupus erythematosus target mitochondrial RNA. Front. Immunol. 10, 1026 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, platelet-derived mitochondria are detectable in the synovial fluid of patients with RA and are present at higher levels than in the synovial fluid of patients with osteoarthritis215, suggesting that the detection of extracellular mitochondria might constitute a new avenue for the development of biomarkers in rheumatic diseases.”

What the sources say

• Supported

  The Results report significant levels of extracellular mitochondria in RA synovial fluid and lower concentrations of platelet-origin mitochondria in osteoarthritis synovial fluid. The proposed biomarker avenue is the citing authors’ inference, not a finding attributed to this source. (LLM, conf=0.93)

  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

“The plasma of patients with SLE contains elevated levels of extracellular vesicle-containing immune complexes compared with healthy individuals, the presence of which is associated with anti-dsDNA antibodies, pro-inflammatory cytokines and disease activity213–217.”

What the sources say

• Partly supported

  The Introduction (page not provided) describes elevated microparticle levels in disease and notes their presence in SLE; the Discussion (page not provided) says circulating microparticles in SLE are associated with autoantibodies. Neither passage establishes elevated levels of microparticle-containing immune complexes in SLE plasma versus healthy plasma, or links those complexes to pro-inflammatory cytokines or disease activity. The paper does not specify an anti-dsDNA association for the complexes. (LLM, conf=0.86)

  cites [213] Cloutier, N. et al. The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes. EMBO Mol. Med. 5, 235–249 (2013). sourceExperimental — accuracy not yet measured
• ?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
• ?Could not verify

  The Methods describe samples from healthy donors and patients with rheumatoid arthritis or osteoarthritis, not an SLE plasma comparison. The Discussion mentions SLE only while speculating about mitochondrial antigens and anticardiolipin antibodies; it does not report elevated vesicle-containing immune complexes or associations with anti-dsDNA antibodies, cytokines, or disease activity. (LLM, conf=0.78)

  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
• ?Not checked — no full text of the sourcecites [216] Fortin, P. R. et al. Distinct subtypes of microparticle-containing immune complexes are associated with disease activity, damage, and carotid intima-media thickness in systemic lupus erythematosus. J. Rheumatol. 43, 2019–2025 (2016). source
• Partly supported

  The Abstract (page unavailable) reports 2–10 times more microparticles in SLE blood than in controls, and the Discussion reports an association between some platelet-derived microparticles and inflammatory receptors. But the Discussion describes immune-complex formation as a possibility, does not establish the claimed association with anti-dsDNA antibodies, and explicitly says the study did not show a relationship between microparticle levels and disease activity. (LLM, conf=0.87)

  cites [217] Mobarrez, F. et al. Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations. Sci. Rep. 6, 36025 (2016). sourceExperimental — accuracy not yet measured

In the paper

“AMA-M2 have several targets; the E2 subunit of the pyruvate dehydrogenase complex-E2 (PDC-E2) being the immunodominant epitope233.”

What the sources say

• Partly supported

  The Introduction (p. 1) identifies PDC-E2 alongside two other AMA-M2 targets, supporting the claim that AMA-M2 has several targets. Neither that passage nor the Discussion (p. 3) identifies PDC-E2 as the immunodominant epitope, so that part is unsupported. (LLM, conf=0.88)

  cites [233] Tomizawa, M. et al. Anti-mitochondrial M2 antibody-positive autoimmune hepatitis. Exp. Ther. Med. 10, 1419–1422 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Mitochondrial antigens presented by MHC II molecules are detectable in tumour cells and in primary biliary cirrhosis (PBC, also called primary biliary cholangitis), suggesting that MHC class II molecules also contribute to pro-inflammatory responses to mitochondrial antigens226,227.”

What the sources say

• ?Not checked — no full text of the sourcecites [226] Qi, L., Rojas, J. M. & Ostrand-Rosenberg, S. Tumor cells present MHC class II-restricted nuclear and mitochondrial antigens and are the predominant antigen presenting cells in vivo. J. Immunol. 165, 5451–5461 (2000). source
• Partly supported

  Section 4 reports MHC class II expression on bile-duct cells in PBC, and sections 7.1–7.2 propose that class II presentation could stimulate an inflammatory immune response. But presentation of mitochondrial peptides in PBC is hypothetical in this paper, not reported as detectable; the passages do not establish the tumour-cell claim. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  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

“Extracellular vesicles, also referred to microparticles, can also contain mitochondria and can associate with antibodies, forming large extracellular vesicle-containing immune complexes213.”

What the sources say

• Partly supported

  The Abstract and the Results section on microparticles and immune complexes describe large, antibody-associated microparticle-containing immune complexes in rheumatoid arthritis synovial fluid. Our copy does not say that the microparticles contain mitochondria (searched: “mitochondria”). Page numbers were not available in the indexed passages. (LLM, conf=0.89)

  cites [213] Cloutier, N. et al. The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes. EMBO Mol. Med. 5, 235–249 (2013). sourceExperimental — accuracy not yet measured

In the paper

“Notably, several studies have reported the presence of similar anti-mitochondrial antibodies in patients with Sjögren syndrome239,240, raising interest in the pathogenic involvement of anti-mitochondrial antibodies in diseases that affect the exocrine glands and epithelia241.”

What the sources say

• ?Not checked — no full text of the sourcecites [239] Fujikura, S. et al. Sjögren’s syndrome and primary biliary cirrhosis: presence of autoantibodies to purified mitochondrial 2-OXO acid dehydrogenases. J. Rheumatol. 17, 1453–1457 (1990).
• ?Not checked — no full text of the sourcecites [240] Skopouli, F. N., Barbatis, C. & Moutsopoulos, H. M. Liver involvement in primary Sjögren’s syndrome. Br. J. Rheumatol. 33, 745–748 (1994). source
• Supported

  The Diagnostic criteria section reports antimitochondrial antibodies in 22% of Sjögren syndrome sera. The Immunopathogenesis section discusses locally produced IgA antimitochondrial antibodies, possible involvement of epithelial tissues, and autoimmune epithelitis. The paper calls the antibodies’ pathogenic role debatable, consistent with the citing sentence’s framing as a question of interest rather than an established mechanism. (LLM, conf=0.88)

  cites [241] Selmi, C., Meroni, P. L. & Gershwin, M. E. Primary biliary cirrhosis and Sjögren’s syndrome: autoimmune epithelitis. J. Autoimmun. 39, 34–42 (2012). source

In the paper

“The detection of the M2 type of anti-mitochondrial antibodies (that is, AMA-M2, often mistakenly referred to as ‘AMA’ by metonymy) is routinely performed in clinical settings as AMA-M2 positivity is a serological criterion for the diagnosis of PBC232.”

What the sources say

• Supported

  Section 3 identifies serum AMA positivity as one of the three diagnostic criteria for PBC. Section 3.1 explains that the epitopes recognized by AMA are often called M2 antigens and says assays for these antigens are widely available and most frequently used by commercial laboratories. (LLM, conf=0.92)

  cites [232] Bowlus, C. L. & Gershwin, M. E. The diagnosis of primary biliary cirrhosis. Autoimmun. Rev. 13, 441–444 (2014). source

In the paper

“Antibodies to mitochondrial 60 kDa heat-shock protein (HSP60), a mitochondrial protein, are increased in patients with SLE and are associated with thrombotic events when concomitantly present with aPL antibodies264,265.”

What the sources say

• ?Could not verify

  The Introduction identifies hsp60 as a mitochondrial protein and an antibody target, but does not report increased anti-hsp60 antibodies in SLE. The Results examine anti-ATP synthase antibodies in SLE sera, not an association of anti-hsp60 antibodies with thrombosis or concomitant aPL antibodies. Searches for those associations found no passage addressing them. (LLM, conf=0.76)

  cites [264] Alard, J.-E. et al. Autoantibodies to endothelial cell surface ATP synthase, the endogenous receptor for hsp60, might play a pathogenic role in vasculatides. PLoS One 6, e14654–e14654 (2011). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [265] Dieudé, M. et al. Autoantibodies to heat shock protein 60 promote thrombus formation in a murine model of arterial thrombosis. J. Thromb. Haemost. 7, 710–719 (2009). source

In the paper

“Both IgG and IgM antibodies that target mtRNA (anti-mtRNA antibodies) are present at higher titres in patients with SLE or APS than in healthy individuals; in patients with SLE, higher titres of anti-mtRNA IgG antibodies are associated with a lower occurrence of carotid plaque and lupus nephritis231,261.”

What the sources say

• Partly supported

  The Results report higher anti-mtRNA IgG and IgM in SLE patients than in healthy controls, but report an increase in APS patients only for IgG; they do not establish the claimed IgM increase in APS. The Results also associate higher IgG with less carotid plaque in bivariate analysis and less lupus nephritis in multivariate analysis, though each association was not significant in the other model. The supplied passages have no page numbers. (LLM, conf=0.88)

  cites [231] Becker, Y. et al. Autoantibodies in systemic lupus erythematosus target mitochondrial RNA. Front. Immunol. 10, 1026 (2019). sourceExperimental — accuracy not yet measured
• ?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

In the paper

“Naturally occurring mitochondrial antibodies are thought to enhance the clearance of mitochondrial components released during cell death and apoptosis63, as indicated by the various negative associations between levels of autoantibodies to mitochondria and clinical parameters of several diseases231,261,269.”

What the sources say

• ?Not checked — no full text of the sourcecites [63] Tuominen, A. et al. A natural antibody to oxidized cardiolipin binds to oxidized low-density lipoprotein, apoptotic cells, and atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 26, 2096–2102 (2006). source
• Partly supported

  Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [231] Becker, Y. et al. Autoantibodies in systemic lupus erythematosus target mitochondrial RNA. Front. Immunol. 10, 1026 (2019). sourceExperimental — accuracy not yet measured
• ?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
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [269] Frostegård, A. G. et al. Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality. Clin. Exp. Immunol. 174, 441–448 (2013). source

In the paper

“IgG antibodies that target mtDNA (anti-mtDNA antibodies) are increased in the sera of patients with SLE compared with healthy individuals and are associated with disease activity and the development of lupus nephritis230.”

What the sources say

• Partly supported

  The Results (Fig. 4) report higher anti-mtDNA antibody levels in SLE sera than in healthy controls. The Results (Table 4) associate these antibodies with a history of lupus nephritis, but find no association with the measured disease-activity outcome (SLEDAI-2K ≥ 4). A history of nephritis does not establish an association with its later development; the Discussion says prospective confirmation is needed. (LLM, conf=0.94)

  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

In the paper

“Additionally, specific mutations in the mitochondrial genome seem geographically or ethnically restricted and thus might be grouped (that is, into haplogroups) to reveal subgroups at increased risks of developing SLE271,272.”

What the sources say

• Supported

  The Abstract describes mtDNA SNP differences between Europeans and Han Chinese and groups those SNPs into haplogroups M and N. The Discussion reports that haplogroup N is associated with higher SLE risk in a subgroup: Han Chinese women whose disease began after age 50. (LLM, conf=0.88)

  cites [271] Tang, Y. et al. Association of mtDNA M/N haplogroups with systemic lupus erythematosus: a case-control study of Han Chinese women. Sci. Rep. 5, 10817 (2015). source
• ?Not checked — no full text of the sourcecites [272] Teng, Y. et al. Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis. Rheumatology, (2021). source

In the paper

“Additionally, mTOR blockade in patients with SLE treated with N-acetylcysteine or rapamycin reduces both pro-inflammatory T cells and disease activity85,260, suggesting that dietary supplementation or drugs that regulate mitochondrial dynamics might constitute novel therapeutic avenues for mitigating autoantibody production in SLE.”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [85] Lai, Z. W. et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 64, 2937–2946 (2012). sourceExperimental — accuracy not yet measured
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [260] Lai, Z. W. et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet 391, 1186–1196 (2018). source

In the paper

“Notably, inhibition of the mTOR pathway by rapamycin restores mitochondrial fission and mitophagy, and prevents aPL antibody production in an MRL/lpr murine model of SLE249.”

What the sources say

• Partly supported

  The Results (page unavailable) report that rapamycin blocked mTORC1 activity, increased Drp1 expression, and suppressed aCL and anti-β2GPI antibodies by 85% and 84% in MRL/lpr mice. The Discussion links Drp1 to mitochondrial fission and possible deficient mitophagy, but the paper does not show that rapamycin restored either process; that part of the claim states an inferred mechanism as an observed result. (LLM, conf=0.87)

  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

In the paper

“Immunoreactivity to intact mitochondria (owing to the presence of anti-whole mitochondria antibodies) is increased in the sera of patients with SLE compared with that of healthy individuals and is associated with increased disease activity230,261,262.”

What the sources say

• Partly supported

  The Results (Figure 3) report increased anti-whole-mitochondria antibodies in SLE sera compared with healthy controls. But the Results (Table 4) do not support the claimed association with increased disease activity: anti-whole-mitochondria antibodies were not significantly associated with high SLEDAI-2K activity (p = 0.57; adjusted p = 0.89). (LLM, conf=0.93)

  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
• ?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 Results (‘Relationship of anti-wMITO and disease activity’; page unavailable) report that antibodies to whole mitochondria are associated with higher SLE disease-activity scores. The Discussion says SLE sera bound well to intact mitochondria, and the Methods list healthy controls, but the retrieved passages do not establish that binding was higher in SLE sera than in healthy sera. (LLM, conf=0.82)

  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

“Haplogroup U, previously associated with severe progression of osteoarthritis47, is enriched in patients with RA compared with healthy individuals45, suggesting that some mtDNA haplogroups increase an individual’s susceptibility to joint disorders”

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 [47] Rego-Perez, I., Fernandez-Moreno, M., Fernandez-Lopez, C., Arenas, J. & Blanco, F. J. Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. Arthritis Rheum. 58, 2387–2396 (2008). source

In the paper

“Defects in mitochondria can be caused by mutations in the mitochondrial genome or by chronic exposure to pro-inflammatory cytokines, including type I interferons”

In the paper

“antibodies can target mitochondria in autoimmune diseases, suggesting an interplay between the adaptive immune system and mitochondria”

In the paper

“haplogroup F1 and its subhaplogroup F1a are negatively associated with the development of RA, and hence are considered protective factors46”

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

“MtDNA is highly polymorphic and has a mutation rate that is 5–10 times higher than nuclear DNA25”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Brown, M. D., Torroni, A., Reckord, C. L. & Wallace, D. C. Phylogenetic analysis of Leber’s hereditary optic neuropathy mitochondrial DNA’s indicates multiple independent occurrences of the common mutations. Hum. Mutat. 6, 311–325 (1995). source

In the paper

“Other abnormalities in T cells in SLE include mitochondrial hyperpolarization and ATP depletion, potentially caused by defective activity of the F0F1–ATP synthase34,73”

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
• ?Not checked — no full text of the sourcecites [73] Kovacs, B., Vassilopoulos, D., Vogelgesang, S. A. & Tsokos, G. C. Defective CD3-mediated cell death in activated T cells from patients with systemic lupus erythematosus: role of decreased intracellular TNF-α. Clin. Immunol. Immunopathol. 81, 293–302 (1996). source

In the paper

“T cells in SLE are characterized by chronic activation and a heavy reliance on oxidative phosphorylation for ATP production, thus increasing mtROS production”

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

“the expression of mitofusin 2 is increased in chondrocytes from patients with OA compared with chondrocytes from healthy individuals and its expression in these cells is associated with a pro-inflammatory metabolic shift from oxidative phosphorylation to glycolysis103”

What the sources say

• ?Not checked — no full text of the sourcecites [103] Xu, L. et al. MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis. Osteoarthritis Cartilage 28, 1079–1091 (2020). source

In the paper

“in in vitro studies, methotrexate, a drug commonly used in rheumatology, can reduce the mitochondrial membrane potential and increase ROS production in synoviocytes, ultimately inducing mitochondria-dependent apoptosis of the cells”

What the sources say

• ?Not checked — no full text of the sourcecites [65] Lee, S. Y. et al. Synoviocyte apoptosis may differentiate responder and non-responder patients to methotrexate treatment in rheumatoid arthritis. Arch. Pharm. Res. 37, 1286–1294 (2014). source

In the paper

“In gout, diets rich in fructose and leucin are associated with hyperuricaemia and the development of monosodium urate crystals, which in turn elicit mitochondrial dysfunction, mtROS production and defective mitophagy95”

What the sources say

• ?Not checked — no full text of the sourcecites [95] Cleophas, M. C., Crişan, T. O. & Joosten, L. A. Factors modulating the inflammatory response in acute gouty arthritis. Curr. Opin. Rheumatol. 29, 163–170 (2017). source

In the paper

“Altered Ca2+ signalling in T cells isolated from patients with SLE is attributed to nitric oxide-induced mitochondrial biogenesis and the formation of megamitochondria113, and potentially leads to defective IL-2 production and inappropriate activation of T cells in SLE114,115”

What the sources say

• ?Not checked — no full text of the sourcecites [113] Nagy, G., Barcza, M., Gonchoroff, N., Phillips, P. E. & Perl, A. Nitric oxide-dependent mitochondrial biogenesis generates Ca2+ signaling profile of lupus T cells. J. Immunol. 173, 3676–3683 (2004). source
• ?Not checked — no full text of the sourcecites [114] Kammer, G. M., Perl, A., Richardson, B. C. & Tsokos, G. C. Abnormal T cell signal transduction in systemic lupus erythematosus. Arthritis Rheum. 46, 1139–1154 (2002). source
• ?Not checked — no full text of the sourcecites [115] Kyttaris, V. C., Juang, Y. T. & Tsokos, G. C. Immune cells and cytokines in systemic lupus erythematosus: an update. Curr. Opin. Rheumatol. 17, 518–522 (2005). source

In the paper

“Mitochondria in T cells from patients with SLE are hyperpolarization, a feature that is associated with glutathione depletion53”

What the sources say

• ?Not checked — no full text of the sourcecites [53] Banki, K., Hutter, E., Gonchoroff, N. J. & Perl, A. Elevation of mitochondrial transmembrane potential and reactive oxygen intermediate levels are early events and occur independently from activation of caspases in Fas signaling. J. Immunol. 162, 1466–1479 (1999). source

In the paper

“These defects might hinder activation-induced cell death, while promoting necrotic cell death, thus resulting in the persistence of autoreactive lymphocytes and the generation of substrates for autoantibodies34,73”

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
• ?Not checked — no full text of the sourcecites [73] Kovacs, B., Vassilopoulos, D., Vogelgesang, S. A. & Tsokos, G. C. Defective CD3-mediated cell death in activated T cells from patients with systemic lupus erythematosus: role of decreased intracellular TNF-α. Clin. Immunol. Immunopathol. 81, 293–302 (1996). source

In the paper

“Mitochondria in T cells from patients with SLE have various defects of the electron transfer chain, which lead to hyperpolarization of the mitochondria, the production of mtROS and downstream dysregulation of apoptosis34,141”

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
• ?Not checked — no full text of the sourcecites [141] Leishangthem, B. D., Sharma, A. & Bhatnagar, A. Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus. Lupus 25, 272–281 (2016). source

In the paper

“In the Jurkat T cell line, incubation with serum from patients with SLE elicits both intrinsic and extrinsic apoptotic pathways; overexpression of BCL-2 inhibits apoptosis, pointing to a notable contribution of the intrinsic pathway in cell death mediated by SLE-related factors140”

What the sources say

• ?Not checked — no full text of the sourcecites [140] Bengtsson, A. A., Gullstrand, B., Truedsson, L. & Sturfelt, G. SLE serum induces classical caspase-dependent apoptosis independent of death receptors. Clin. Immunol. 126, 57–66 (2008). source

In the paper

“hypoxia and reoxygenation of fibroblast-like synoviocytes (an important contributor to inflammatory joint diseases such as RA and osteoarthritis) promotes mitochondrial permeabilization and ROS release in these cells, which activates downstream pro-inflammatory pathways142”

What the sources say

• ?Not checked — no full text of the sourcecites [142] Zhou, S., Wen, H., Cai, W., Zhang, Y. & Li, H. Effect of hypoxia/reoxygenation on the biological effect of IGF system and the inflammatory mediators in cultured synoviocytes. Biochem. Biophys. Res. Commun. 508, 17–24 (2019). source

In the paper

“In a simian model of RA, a complex of RIPK1 and voltage-dependent anion channel 1 (VDAC1; a major component of the mitochondrial outer membrane) triggers apoptosis in cardiomyocytes, which might explain various cardiovascular manifestations in this disease139”

What the sources say

• ?Not checked — no full text of the sourcecites [139] Zeng, F. et al. Central role of RIPK1-VDAC1 pathway on cardiac impairment in a non-human primate model of rheumatoid arthritis. J. Mol. Cell Cardiol. 125, 50–60 (2018). source