Mitochondria in the Regulation of Innate and Adaptive Immunity
Open accessAbstract
Summary Mitochondria are well appreciated for their role as biosynthetic and bioenergetic organelles. In the past two decades, mitochondria have emerged as signaling organelles that contribute critical decisions about cell proliferation, death and differentiation. Mitochondria not only sustain immune cell phenotypes but also are necessary for establishing immune cell phenotype and their function. Mitochondria can rapidly switch from primarily being catabolic organelles generating ATP to anabolic organelles that generate both ATP and building blocks for macromolecule synthesis. This enables them to fulfill appropriate metabolic demands of different immune cells. Mitochondria have multiple mechanisms that allow them to activate signaling pathways in the cytosol including altering in AMP/ATP ratio, the release of ROS and TCA cycle metabolites, as well as the localization of immune regulatory proteins on the outer mitochondrial membrane. In this Review, we discuss the evidence and mechanisms that mitochondrial dependent signaling controls innate and adaptive immune responses.
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Written from the paper’s full text.
TL;DR
This review argues that mitochondria are not only bioenergetic and biosynthetic organelles but also signaling hubs that shape innate and adaptive immune cell fate and function. It synthesizes evidence that mitochondrial ROS, TCA-cycle metabolites, and outer-membrane scaffolding regulate macrophage polarization, inflammasome/RLR antiviral responses, T cell activation/differentiation, and memory T cell formation.
Key findings
- Mitochondria balance ATP production and biosynthesis: oxidation of pyruvate and palmitate generates 31.5 and 113 ATP, respectively, compared with 2 ATP from glycolysis; TCA-cycle intermediates also support macromolecule synthesis and signaling.
- Mitochondrial ROS and metabolites regulate innate immunity: TLR signaling can increase mitochondrial ROS for bactericidal activity, succinate stabilizes HIF-1α to induce IL-1β, and mitochondrial ROS, oxidized mtDNA, and cardiolipin promote NLRP3 inflammasome activation.
- Mitochondrial outer-membrane localization is required for RLR antiviral signaling via MAVS, including at mitochondrial-associated ER membranes; mitochondrial dynamics and membrane potential also influence RLR signaling.
- Adaptive immunity depends on mitochondrial metabolism: T cell activation requires mitochondrial ROS for optimal NFAT, NF-κB, and proximal TCR signaling; Tregs rely on AMPK-dependent fatty acid oxidation, Th17 cells on glycolysis and de novo fatty acid synthesis, and CD8+ memory T cells on fatty acid oxidation/spare respiratory capacity fueled by lysosomal lipolysis.
Methods
- Narrative review; no primary experimental design, sample, or statistical analysis is reported. The authors synthesize published literature on mitochondrial signaling in innate and adaptive immune cells.
Limitations
- Stated: the authors note that several mechanisms discussed lack in vivo evidence and call for future genetic and targeted small-molecule studies in complex organismal immune responses.
- Stated: mechanistic details remain unresolved, including critical mitochondrial ROS targets, how peroxisomes, ER, and mitochondria communicate, and whether TCA intermediates such as acetyl-CoA, α-ketoglutarate, and citrate alter immune activation like succinate.
- Evident: as a narrative review, it does not provide systematic search methods or primary data; the authors also note that pharmacologic inhibition can affect multiple cell types and make conclusions difficult to interpret.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
0 of 40 cited sources checked · 0 supported · 0 flagged
- Premisecitation
MAVS localization to the outer mitochondrial membrane is indispensable for its function in RLR signaling.
“A breakthrough in establishing the role for mitochondria in RLR-activated antiviral immunity was the identification of the RLR mitochondrial adaptor protein MAVS (mitochondrial antiviral-signaling protein)(Kawai et al., 2005; Meylan et al., 2005; Seth et al., 2005; Xu et al., 2005) localization to the outer mitochondrial membrane is indispensable for its function.”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationnone given
Mitochondria act as signaling organelles that influence cell proliferation, death, and differentiation.
“Mitochondria are well appreciated for their role as biosynthetic and bioenergetic organelles. In the past two decades, mitochondria have emerged as signaling organelles that contribute critical decisions about cell proliferation, death and differentiation.”
Quote in the paperSubstantial claim - Premisecitation
Inhibiting fatty acid oxidation with etomoxir reduces EAE disease severity.
“unexpectedly fatty acid oxidation inhibition by etomoxir reduces disease severity of EAE (Shriver and Manchester, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shriver and Manchester, 2011
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- Interpretationreasoning
Mitochondria are central metabolic hubs necessary for both maintenance and establishment of immune cell phenotypes.
“Mitochondria are central hubs of metabolism thus have emerged to be necessary for both the maintenance and establishment of immune cell phenotypes.”
Quote in the paperSubstantial claim - Interpretationreasoning
Collectively, the cited metabolic studies suggest that mitochondrial function controls the balance between inflammatory and suppressive CD4+ T helper lineages.
“Nevertheless, collectively these emerging metabolic studies suggest that mitochondrial metabolism function dictates the different inflammatory and suppressive CD4+ T helper lineages.”
Quote in the paperSubstantial claim
- Premisecitation
The fatty acids used by Tm cells come from internal lysosomal stores rather than extracellular sources.
“The source of fatty acids in Tm cells is not extracellular, but rather internal lysosomal stores.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites O'Sullivan et al., 2014
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- Interpretationnone given
Mitochondria can switch from catabolic ATP production to anabolic metabolism that also supplies macromolecule precursors, matching immune cell demands.
“Mitochondria can rapidly switch from primarily being catabolic organelles generating ATP to anabolic organelles that generate both ATP and building blocks for macromolecule synthesis. This enables them to fulfill appropriate metabolic demands of different immune cells.”
Quote in the paperSubstantial claim - Premisecitation
Increased mitochondrial metabolism in Tregs is due to increased AMPK-dependent fatty acid oxidation.
“This increased mitochondrial metabolism in Tregs was found to be due to increased AMPK-dependent fatty acid oxidation (MacIver et al., 2011; Michalek et al., 2011).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Th17 cells engage in de novo fatty acid synthesis necessary for the Th17 phenotype.
“By contrast, Th17 cells engage in de novo fatty acid synthesis that is necessary for the Th17 phenotype.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Berod et al., 2014 source
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- Interpretationreasoning
The review argues that signaling dependent on mitochondria governs both innate and adaptive immunity.
“In this Review, we discuss the evidence and mechanisms that mitochondrial dependent signaling controls innate and adaptive immune responses.”
Quote in the paperSubstantial claim - Interpretationreasoning
Mitochondrial DAMPs drive hyperactivation of innate immunity without microbial infection, i.e., sterile inflammation.
“Thus, mitochondrial DAMPS drive hyperactivation of innate immunity in an absence of an infection by a microorganisms i.e. sterile inflammation.”
Quote in the paperSubstantial claim - Interpretationcitation
Other molecules derived from mitochondria also contribute importantly to B cell activation and effector function.
“Along with ROS signaling, new studies also suggest that other mitochondrial-derived molecules have important roles in B cell activation and effector function.”
Quote in the paperNot a substantial claim - Premisecitation
Activated B cells greatly increase glucose and glutamine metabolism during clonal expansion, similar to T cells.
“Upon activation, B cells greatly enhance glucose and glutamine metabolism during clonal expansion comparable to T cells (Doughty et al., 2006; Garcia-Manteiga et al., 2011; Le et al., 2012).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Doughty et al., 2006 source
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- cites Garcia-Manteiga et al., 2011 source
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- cites Le et al., 2012
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- Rests on an assumption: B cells undergo major metabolic transitions as they move from naïve quiescent cells to anabolic proliferative cells.
- Premisecitation
Plasma cell differentiation requires mitochondrial citrate to be converted to acetyl-CoA and oxaloacetate in the cytoplasm.
“Recent studies have suggested that plasma cells produce increased levels of phospholipids when compared to naïve B cells, and plasma cell differentiation is dependent on mitochondrial citrate conversion to acetyl-CoA and oxaloacetate in the cytoplasm (Dufort et al., 2014; Fagone et al., 2007).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Tm cells use lysosomal acid lipase (LAL) to free fatty acids from storage for mitochondrial fatty acid oxidation.
“Tm cells utilize lysosomal acid lipase (LAL) in Tm cells to liberate free fatty acids from storage for the robust fatty acid oxidation in the mitochondria.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites O'Sullivan et al., 2014
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- Interpretationcitation
Cellular metabolism actively helps determine the fate of immune cells.
“It is becoming clear that cellular metabolism plays a highly active role in determining cellular destiny in the immune system—in other words, we are learning that the immune cell is what it eats.”
Quote in the paperSubstantial claim - Premisecitation
B cell receptor (BCR) activation is regulated by ROS.
“Along with these changes in metabolism, B cell receptor (BCR) activation is regulated by ROS (Capasso et al., 2010; Singh et al., 2005).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Plasma cells contain more phospholipids than naïve B cells.
“Recent studies have suggested that plasma cells produce increased levels of phospholipids when compared to naïve B cells, and plasma cell differentiation is dependent on mitochondrial citrate conversion to acetyl-CoA and oxaloacetate in the cytoplasm (Dufort et al., 2014; Fagone et al., 2007).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Long-term increases in ROS, possibly from mitochondrial ROS production, are needed for downstream BCR signaling and proliferation after BCR cross-linking.
“Instead, long term elevations in ROS levels, potentially driven by increased production of mitochondrial ROS, are required for downstream BCR signaling and cellular proliferation in response to BCR cross-linking (Wheeler and Defranco, 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wheeler and Defranco, 2012
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- Premisecitation
In primary B cells, early ROS production by NADPH oxidases is not required for BCR signaling.
“However, new data from primary B cells suggests that early ROS production by NADPH oxidases is dispensable for BCR signaling (Richards and Clark, 2009; Wheeler and Defranco, 2012).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Richards and Clark, 2009
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- cites Wheeler and Defranco, 2012
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- Premisecitation
Metformin's anti-tumor effects occur through inhibition of mitochondrial complex I.
“It is not clear what the target of metformin in immune cells is but the anti-tumor effects of metformin are through inhibiting mitochondrial complex I (Wheaton et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wheaton et al., 2014 source
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- Premisecitation
Metformin is being used as an immunomodulator for tuberculosis.
“For example, the anti-diabetic drug metformin is being utilized an immunomodulator for tuberculosis (Singhal et al., 2014).”
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- Premisecitation
In multiple bone marrow transplant models, Bz-423, which inhibits mitochondrial ATP synthase, stopped established graft-versus-host disease while leaving hematopoietic engraftment and lymphocyte reconstitution intact.
“Moreover, Bz-423, a small-molecule inhibitor of the mitochondrial ATP-synthase, arrested established graft versus host disease (GVHD) in several bone marrow transplant models without affecting hematopoietic engraftment or lymphocyte reconstitution (Gatza et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gatza et al., 2011 source
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- Interpretationreasoning
Mitochondrial signals appear necessary for immune cells to carry out their specific roles in innate and adaptive responses to various pathogens.
“Mitochondrial signals appear to be necessary for the immune cell to fulfill its specific role in the immune response in both innate and adaptive settings to a variety of intruders.”
Quote in the paperSubstantial claim
- May combine two claims. 18
May combine two claims.
PremisecitationMitochondrial fusion promotes RLR signaling, whereas mitochondrial fission inhibits it.
“Multiple studies have demonstrated that mitochondrial fusion promotes, whereas mitochondrial fission inhibits RLR signaling (Castanier et al., 2010; Yasukawa et al., 2009; Zhao et al., 2012).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationMemory CD8+ T cells (Tm) contain more mitochondria and have greater spare respiratory capacity, supported by fatty acid oxidation for ATP production.
“Tm cells display increased mitochondrial number and spare respiratory capacity, which is fueled by fatty acid oxidation to generate copious amount of ATP (Pearce et al., 2009; van der Windt et al., 2012).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Pearce et al., 2009 source
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- cites van der Windt et al., 2012 source
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- Rests on an assumption: Fatty acid oxidation yields nearly three times as much ATP as mitochondrial glucose oxidation.
May combine two claims.
PremisecitationMitochondrial ROS regulate metabolic adaptation, differentiation, and proliferation.
“Recent studies indicate that mitochondrial ROS regulate metabolic adaptation, differentiation and proliferation (Sena and Chandel, 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sena and Chandel, 2012 source
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InterpretationcitationM2 macrophage polarization requires mitochondrial fatty acid oxidation, and inhibiting CPT1 with etomoxir blocks classic M2 gene expression.
“The carnitine palmitoyltransferase-1 (CPT1) inhibitor etomoxir, which inhibits fatty acid translocation into the mitochondria, is sufficient to inhibit expression of classic M2 genes indicating that the increase in mitochondrial metabolism is not simply an effect of STAT6 activation needed for sustaining the M2 phenotype, but is in fact a driver of M2 macrophage activation and function.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The M1/M2 macrophage classification, though imperfect, is a useful model for studying metabolic differences between macrophages with different functions.
May combine two claims.
PremisecitationMitochondrial ROS are necessary for optimal NLRP3 inflammasome activation, though calcium influx and potassium efflux also regulate it.
“It is important to note that mitochondrial ROS are necessary for optimal activation of NLRP3 inflammasome as other key activators such as influx of calcium and potassium efflux are also major regulators of NLRP3 inflammasome (Gurung et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gurung et al., 2014
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Interpretationnone givenMitochondria activate cytosolic signaling by changing AMP/ATP ratio, releasing ROS and TCA cycle metabolites, and placing immune regulatory proteins on the outer mitochondrial membrane.
“Mitochondria have multiple mechanisms that allow them to activate signaling pathways in the cytosol including altering in AMP/ATP ratio, the release of ROS and TCA cycle metabolites, as well as the localization of immune regulatory proteins on the outer mitochondrial membrane.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationTregs have elevated oxidative phosphorylation and decreased glycolytic flux compared with Th17 cells.
“Tregs have elevated levels of oxidative phosphorylation and decreased glycolytic flux compared to Th17 cells (Michalek et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Michalek et al., 2011 source
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May combine two claims.
InterpretationreasoningMetabolism not only sustains immune cell phenotypes but also feeds back to alter signaling and drive those phenotypes.
“An emerging concept is that metabolism not only sustains diverse immune cell phenotypes as a consequence of alterations in cellular signaling, but metabolism also feeds back and alters signaling to drive immune cell phenotypes.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenMitochondria are required both to maintain and to establish immune cell phenotypes and functions.
“Mitochondria not only sustain immune cell phenotypes but also are necessary for establishing immune cell phenotype and their function.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationTm cells express less surface CD36 than effector T cells and carry out de novo lipogenesis, storing lipids in lysosomes.
“Tm cells display reduced surface expression of CD36, necessary for fatty acid uptake, compared with Te cells and engage in de novo lipogenesis and store lipids in lysosomes (O'Sullivan et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites O'Sullivan et al., 2014
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PremisecitationBCR ligation causes calcium release into the cytoplasm, promoting ROS production and inactivation of receptor-coupled phosphatases, which allows downstream signaling pathways to activate.
“Specifically, BCR ligation stimulates calcium release into the cytoplasm that promotes ROS production and inactivation of receptor-coupled phosphates, allowing for activation of downstream signaling pathways.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Singh et al., 2005 source
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PremisecitationThe size of the ROS pulse determines how long BCR signaling lasts and how strongly downstream pathways are activated.
“Depending on the magnitude of the ROS pulse, there is increased duration of BCR signaling and enhanced activation of downstream signaling pathways (Singh et al., 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Singh et al., 2005 source
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PremisecitationReducing or increasing AMPK, a positive regulator of fatty acid oxidation, respectively decreases or increases memory T cell formation.
“The importance of fatty acid oxidation for Tm cells is bolstered by the observations that diminishing or enhancing AMPK, a positive regulator of fatty acid oxidation, decreases or increases formation of memory T cells (MacIver et al., 2011; Pearce et al., 2009; Rolf et al., 2013; Tamás et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningTm cells appear to run a futile cycle in which fatty acid synthesis and oxidation occur simultaneously, and this cycle is needed to maintain memory T cells.
“Thus, Tm cells appear to utilize a “futile cycle” whereby fatty acid synthesis occurs concurrently with fatty acid oxidation, which is required for proper maintenance of memory T cells.”
Quote in the paperSubstantial claim- Rests on an assumption: Fatty acid oxidation yields nearly three times as much ATP as mitochondrial glucose oxidation.
- Rests on an assumption: Memory T cells are not rapidly proliferating, have low anabolic needs, and catabolize nutrients to ATP for long-term survival.
May combine two claims.
Interpretationnone givenIn immune cells, mitochondria contribute to signaling by producing ROS, by making metabolites available, and by serving as physical scaffolds for protein interactions.
“We outline that in immune cells, mitochondria participate in signaling through ROS production, metabolite availability, and by physically acting as scaffolding for protein interaction.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThese studies indicate that mitochondrial metabolism changes during B cell activation and plasma cell development.
“Although the evidence is incomplete, these new studies indicate that mitochondrial metabolism is altered during B cell activation and plasma cell development.”
Quote in the paperSubstantial claim- Rests on an assumption: B cells undergo major metabolic transitions as they move from naïve quiescent cells to anabolic proliferative cells.
May combine two claims.
PremisecitationRecent work indicates that signals traveling from the cell surface to the nucleus frequently take detours via metabolic machinery, so metabolism participates in cell fate choices.
“While decades of study have shown that direct signaling from the cell surface to the nucleus is critical to these cell fate decisions, more recent work has shown that these signaling pathways often include detours that transmit through metabolic machinery to ensure cooperation of metabolism in the cell fate decision (Pearce et al., 2013)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pearce et al., 2013
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PremisecitationIncreasing or decreasing glycolytic flux, which reciprocally modulates mitochondrial metabolism, respectively enhances or diminishes memory T cell generation.
“Further evidence supporting the importance of mitochondrial metabolism comes from the observation that increasing or decreasing glycolytic flux, which reciprocally modulates mitochondrial metabolism, results in enhanced or diminished generation of memory T cells, respectively (Sukumar et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sukumar et al., 2013 source
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The authors state this as an assumption.
The M1/M2 macrophage classification, though imperfect, is a useful model for studying metabolic differences between macrophages with different functions.
“Although this classification scheme is imperfect and there almost certainly exists many more macrophage subtypes, it is a useful model for studying how metabolism differs in macrophages with differing functions (Mosser and Edwards, 2008).”
The authors state this as an assumption.
Dendritic cells can be simplified into immunogenic and tolerant subsets for the purpose of discussing their metabolism.
“As with macrophages, DCs likely exist in numerous different subsets however for simplicity that are classically designated as either an immunogenic or tolerant subset.”
The paper relies on this without support.
Fatty acid oxidation yields nearly three times as much ATP as mitochondrial glucose oxidation.
“Fatty acid oxidation generates almost 3 times more ATP than glucose oxidation by mitochondria, thus it is robust mechanism to generate ATP.”
The paper relies on this without support.
Memory T cells are not rapidly proliferating, have low anabolic needs, and catabolize nutrients to ATP for long-term survival.
“Tm cells are not rapidly proliferating and thus do not have high anabolic requirements. They efficiently catabolize nutrients to generate ATP to maintain long-term cell survival.”
The paper relies on this without support.
B cells undergo major metabolic transitions as they move from naïve quiescent cells to anabolic proliferative cells.
“Similar to T cells, B cells also undergo major transitions in their metabolic profiles as they transition from naïve quiescent cells to anabolic proliferative cells.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cardiolipin, N-formylated peptides, mtDNA, ATP and reactive oxygen species are known mitochondrial damage-associated molecular patterns.
“Cardiolipin, N-formylated peptides, mtDNA, ATP and reactive oxygen species are known mitochondrial damage-associated molecular patterns (9, 28–30).”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [28]
In the section on mitochondrial signaling and innate immunity (page unavailable), the paper explicitly identifies mtDNA and N-formyl peptides as mitochondrial DAMPs and reports that cardiolipin activates NLRP3. It lists ATP among DAMPs but does not identify it as a mitochondrial DAMP; it describes mitochondrial ROS as an inflammatory signaling factor, not as a DAMP. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMitochondria and their components, such as N-formylated peptides and mtDNA, are recognized as damage-associated molecular patterns that activate innate immunity and elicit inflammation.
“Mitochondria and their components (e.g. N-formylated peptides and mtDNA) are recognized as damage-associated molecular patterns (DAMPs), which activate the innate immune system and elicit an inflammatory response6,21–23.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [21]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Direction of glycolysis effect on memory T cells is reversed
MajorThe text says increasing glycolytic flux enhances memory T-cell generation, but the cited study's title says inhibiting glycolytic metabolism enhances CD8+ T-cell memory.
“Further evidence supporting the importance of mitochondrial metabolism comes from the observation that increasing or decreasing glycolytic flux, which reciprocally modulates mitochondrial metabolism, results in enhanced or diminished generation of memory T cells, respectively (Sukumar et al., 2013).”
“100. Sukumar M Liu J Ji Y Subramanian M Crompton JG Yu Z Roychoudhuri R Palmer DC Muranski P Karoly ED 2013 Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function J Clin Invest 123 4479 4488 24091329 PMC3784544”
Memory T cells are said to contrast with themselves
MinorThe sentence compares Tm cells with Tm cells, even though the section distinguishes memory T cells (Tm) from effector T cells (Te). A cell population cannot have a contrasting metabolic profile relative to itself.
“Thus, Tm cells have a contrasting metabolic profile compared to Tm cells.”
“During the resolution phase of an infection, the majority of CD8+ Te cells undergo cell death with the survival of a few long-lived CD8+ memory T cells (Tm).”
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“They further activate cells through nuclear oligomerization domain-like receptors (28, 29, 31), toll-like receptors (TLR) (e.”
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- Authors
- Weinberg, S. E., Sena, L. A., & Chandel, N. S.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Chandel, Navdeep S.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 42
- Issue
- 3
- Pages
- 406-417
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4365295
- OpenAlex
- W2005853038
- Semantic Scholar
- 13bde7eb931e0d08aa2d615e101d31c6debcb3f8
- Cited by
- 960
- References
- 124
- Citations by year
- 2026: 76 · 2025: 80 · 2024: 107 · 2023: 91 · 2022: 96 · 2021: 128 · 2020: 105 · 2019: 94 · 2018: 58 · 2017: 59 · 2016: 44 · 2015: 20
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL12206201, P01HL071643, R01HL122062, T32HL076139)
- National Cancer Institute (R01CA123067, P30CA060553, T32CA009560)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- mitochondria, mitochondrial signaling, innate immunity, adaptive immunity, immune cell metabolism, AMP/ATP ratio, reactive oxygen species, TCA cycle metabolites, mitochondrial outer membrane, immune cell differentiation, cell proliferation and death
- MeSH terms
- Adenosine Triphosphate, Animals, Citric Acid Cycle, Gene Expression Regulation, Humans, Immunity, Innate, Lymphocytes, Macrophages, Mitochondria, Oxidative Phosphorylation, Signal Transduction, Cytokines, Mitochondrial Proteins, Adaptive Immunity, Inflammasomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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