Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Why succinate? Physiological regulation by a mitochondrial coenzyme Q sentinel

Abstract

Metabolites once considered solely in catabolism or anabolism turn out to have key regulatory functions. Among these, the citric acid cycle intermediate succinate stands out owing to its multiple roles in disparate pathways, its dramatic concentration changes and its selective cell release. Here we propose that succinate has evolved as a signaling modality because its concentration reflects the coenzyme Q (CoQ) pool redox state, a central redox couple confined to the mitochondrial inner membrane. This connection is of general importance because CoQ redox state integrates three bioenergetic parameters: mitochondrial electron supply, oxygen tension and ATP demand. Succinate, by equilibrating with the CoQ pool, enables the status of this central bioenergetic parameter to be communicated from mitochondria to the rest of the cell, into the circulation and to other cells. The logic of this form of regulation explains many emerging roles of succinate in biology, and suggests future research questions.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Mitochondrial bioenergetics and the coenzyme Q (CoQ) pool.
Fig. 2: Succinate controls mitochondrial superoxide production through mitochondrial complex I.
Fig. 3: Accumulated mitochondrial succinate regulates cellular αKG-dependent dioxygenases.
Fig. 4: pH-gated succinate secretion regulates systemic physiology.
Fig. 5: Logic of succinate as a local and systemic bioenergetic sensor.

References

  1. Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  2. Murphy, M. P. & O’Neill, L. A. J. Krebs cycle reimagined: the emerging roles of succinate and itaconate as signal transducers. Cell 174, 780–784 (2018).

    CAS  PubMed  Article  Google Scholar 

  3. Winther, S., Trauelsen, M. & Schwartz, T. W. Protective succinate-SUCNR1 metabolic stress signaling gone bad. Cell Metab. 33, 1276–1278 (2021).

    CAS  PubMed  Article  Google Scholar 

  4. Chandel, N. S. Evolution of mitochondria as signaling organelles. Cell Metab. 22, 204–206 (2015).

    CAS  PubMed  Article  Google Scholar 

  5. Nicholls, D. G. & Ferguson, S. J. Bioenergetics 3rd edn, 31–55 (Academic Press, 2003).

  6. Majmundar, A. J., Wong, W. J. & Simon, M. C. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40, 294–309 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Mihaylova, M. M. & Shaw, R. J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 1016–1023 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Efeyan, A., Comb, W. C. & Sabatini, D. M. Nutrient-sensing mechanisms and pathways. Nature 517, 302–310 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. Stefely, J. A. & Pagliarini, D. J. Biochemistry of mitochondrial coenzyme Q biosynthesis. Trends Biochem. Sci. 42, 824–843 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Lester, R. L., Crane, F. L. & Hatefi, Y. Coenzyme Q: a new group of quinones. J. Am. Chem. Soc. 80, 4751–4752 (1958).

    CAS  Article  Google Scholar 

  11. Rebstock, A. S., Mongin, F., Trecourt, F. & Queguiner, G. Metallation of pyridines and quinolines in the presence of a remote carboxylate group. New syntheses of heterocyclic quinones. Org. Biomol. Chem. 2, 291–295 (2004).

    CAS  PubMed  Article  Google Scholar 

  12. Wang, Y. & Hekimi, S. Understanding ubiquinone. Trends Cell Biol. 26, 367–378 (2016).

    CAS  PubMed  Article  Google Scholar 

  13. Rich, P. R. & Maréchal, A. The mitochondrial respiratory chain. Essays Biochem. 47, 1–23 (2010).

    CAS  PubMed  Article  Google Scholar 

  14. Mitchell, P. Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain: protonmotive ubiquinone cycle. FEBS Lett. 56, 1–6 (1975).

    CAS  PubMed  Article  Google Scholar 

  15. Walker, J. E. The ATP synthase: the understood, the uncertain and the unknown. Biochem. Soc. Trans. 41, 1–16 (2013).

    CAS  PubMed  Article  Google Scholar 

  16. Sun, F. et al. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121, 1043–1057 (2005).

    CAS  PubMed  Article  Google Scholar 

  17. Burger, N. et al. A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo. Free Radic. Biol. Med. 147, 37–47 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Zhang, J. et al. Accumulation of succinate in cardiac ischemia primarily occurs via canonical krebs cycle activity. Cell Rep. 23, 2617–2628 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Reddy, A. et al. pH-gated succinate secretion regulates muscle remodeling in response to exercise. Cell 183, 62–75.e17 (2020). This paper demonstrated protonation-dependent secretion of succinate via MCT1.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Chouchani, E. T. et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515, 431–435 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Kumar, R. et al. A redox cycle with complex II prioritizes sulfide quinone oxidoreductase dependent H2S oxidation. J. Biol. Chem. 298, 101435 (2021).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  22. Spinelli, J. B. et al. Fumarate is a terminal electron acceptor in the mammalian electron transport chain. Science 374, 1227–1237 (2021).

    CAS  PubMed  Article  Google Scholar 

  23. Mills, E. L. et al. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature 560, 102–106 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496, 238–242 (2013). This paper defined succinate accumulation as an upstream metabolite regulator of inflammatory cytokine production.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. Murphy, M. P. How mitochondria produce reactive oxygen species. Biochem. J. 417, 1–13 (2009).

    CAS  PubMed  Article  Google Scholar 

  26. Hinkle, P. C., Butow, R. A., Racker, E. & Chance, B. Partial resolution of the enzymes catalyzing oxidative phosphorylation. XV. Reverse electron transfer in the flavin-cytochrome b region of the respiratory chain of beef heart submitochondrial particles. J. Biol. Chem. 242, 5169–5173 (1967).

    CAS  PubMed  Article  Google Scholar 

  27. Kussmaul, L. & Hirst, J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl Acad. Sci. USA 103, 7607–7612 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. Hirst, J., King, M. S. & Pryde, K. R. The production of reactive oxygen species by complex I. Biochem. Soc. Trans 36, 976–980 (2008). This paper illustrated the mechanism of superoxide production by mitochondrial complex I at the FMN site.

    CAS  PubMed  Article  Google Scholar 

  29. Agip, A.-N. A., Blaza, J. N., Fedor, J. G. & Hirst, J. Mammalian respiratory complex I through the lens of cryo-EM. Annu. Rev. Biophys. 48, 165–184 (2019).

    CAS  PubMed  Article  Google Scholar 

  30. Pryde, K. R. & Hirst, J. Superoxide is produced by the reduced flavin in mitochondrial complex I: a single, unified mechanism that applies during both forward and reverse electron transfer. J. Biol. Chem. 286, 18056–18065 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Goncalves, R. L., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M. & Brand, M. D. Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. J. Biol. Chem. 290, 209–227 (2015).

    CAS  PubMed  Article  Google Scholar 

  32. Chance, B. & Hollunger, G. The interaction of energy and electron transfer reactions in mitochondria. I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J. Biol. Chem. 236, 1534–1543 (1961).

    CAS  PubMed  Article  Google Scholar 

  33. Krishnamoorthy, G. & Hinkle, P. C. Studies on the electron transfer pathway, topography of iron-sulfur centers, and site of coupling in NADH-Q oxidoreductase. J. Biol. Chem. 263, 17566–17575 (1988).

    CAS  PubMed  Article  Google Scholar 

  34. Cino, M. & Del Maestro, R. F. Generation of hydrogen peroxide by brain mitochondria: the effect of reoxygenation following postdecapitative ischemia. Arch. Biochem. Biophys. 269, 623–638 (1989).

    CAS  PubMed  Article  Google Scholar 

  35. Lambert, A. J. & Brand, M. D. Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I). J. Biol. Chem. 279, 39414–39420 (2004).

    CAS  PubMed  Article  Google Scholar 

  36. Yin, Z. et al. Structural basis for a complex I mutation that blocks pathological ROS production. Nat. Commun. 12, 707 (2021).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Tyler, D. D. Polarographic assay and intracellular distribution of superoxide dismutase in rat liver. Biochemical J. 147, 493–504 (1975).

    CAS  Article  Google Scholar 

  38. Sena, L. A. & Chandel, N. S. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 48, 158–167 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Cox, A. G., Winterbourn, C. C. & Hampton, M. B. Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem. J. 425, 313–325 (2009).

    PubMed  Article  CAS  Google Scholar 

  40. Reczek, C. R. & Chandel, N. S. ROS-dependent signal transduction. Curr. Opin. Cell Biol. 33, 8–13 (2015).

    CAS  PubMed  Article  Google Scholar 

  41. Holmstrom, K. M. & Finkel, T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat. Rev. Mol. Cell Biol. 15, 411–421 (2014).

    CAS  PubMed  Article  Google Scholar 

  42. Murphy, M. P. et al. Unraveling the biological roles of reactive oxygen species. Cell Metab. 13, 361–366 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Lennicke, C. & Cochemé, H. M. Redox metabolism: ROS as specific molecular regulators of cell signaling and function. Mol. Cell 81, 3691–3707 (2021).

    CAS  PubMed  Article  Google Scholar 

  44. Brand, M. D. et al. Suppressors of superoxide-H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia-reperfusion injury. Cell Metab. 24, 582–592 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256–4265 (2016).

    CAS  PubMed  Article  Google Scholar 

  46. Mills, E. L. et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167, 457–470.e13 (2016). This paper defined succinate accumulation as an upstream metabolite regulator of inflammatory cytokine production via mitochondrial ROS production.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).

    CAS  PubMed  Article  Google Scholar 

  48. Muzik, O., Mangner, T. J., Leonard, W. R., Kumar, A. & Granneman, J. G. Sympathetic innervation of cold-activated brown and white fat in lean young adults. J. Nucl. Med. 58, 799–806 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. Lettieri Barbato, D. et al. Glutathione decrement drives thermogenic program in adipose cells. Sci. Rep. 5, 13091 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. Ro, S. H. et al. Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species. Proc. Natl Acad. Sci. USA 111, 7849–7854 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. Chouchani, E. T. et al. Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature 532, 112–116 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. Han, Y. H. et al. Adipocyte-specific deletion of manganese superoxide dismutase protects from diet-induced obesity through increased mitochondrial uncoupling and biogenesis. Diabetes 65, 2639–2651 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. Schneider, K. et al. Increased energy expenditure, Ucp1 expression, and resistance to diet-induced obesity in mice lacking nuclear factor-erythroid-2-related transcription factor-2 (Nrf2). J. Biol. Chem. 291, 7754–7766 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. Lee, S. J., Kim, S. H., Park, K. M., Lee, J. H. & Park, J. W. Increased obesity resistance and insulin sensitivity in mice lacking the isocitrate dehydrogenase 2 gene. Free Radic. Biol. Med. 99, 179–188 (2016).

    CAS  PubMed  Article  Google Scholar 

  55. Chouchani, E. T., Kazak, L. & Spiegelman, B. M. Mitochondrial reactive oxygen species and adipose tissue thermogenesis: bridging physiology and mechanisms. J. Biol. Chem. 292, 16810–16816 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Kazak, L. et al. UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction. Proc. Natl Acad. Sci. USA 114, 7981–7986 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. Sanchez-Alavez, M., Bortell, N., Galmozzi, A., Conti, B. & Marcondes, M. C. Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice. Temperature 1, 227–241 (2014).

    Article  Google Scholar 

  58. Sanchez-Alavez, M. et al. ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia. Front. Endocrinol. 4, 44 (2013).

    CAS  Article  Google Scholar 

  59. Jedrychowski, M. P. et al. Facultative protein selenation regulates redox sensitivity, adipose tissue thermogenesis, and obesity. Proc. Natl Acad. Sci. USA 117, 10789–10796 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. Mills, E. L. et al. Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation. Cell Metab. 34, 140–157.e8 (2022).

    CAS  PubMed  Article  Google Scholar 

  61. Xiao, H. et al. A quantitative tissue-specific landscape of protein redox regulation during aging. Cell 180, 968–983.e24 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. Fernández-Agüera, M. C. et al. Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling. Cell Metab. 22, 825–837 (2015).

    PubMed  Article  CAS  Google Scholar 

  63. Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11, 298–300 (1956).

    CAS  PubMed  Article  Google Scholar 

  64. Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. Ristow, M. Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits. Nat. Med. 20, 709–711 (2014).

    CAS  PubMed  Article  Google Scholar 

  66. Schulz, T. J. et al. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6, 280–293 (2007).

    CAS  PubMed  Article  Google Scholar 

  67. Scialò, F. et al. Mitochondrial ROS produced via reverse electron transport extend animal lifespan. Cell Metab. 23, 725–734 (2016). This paper demonstrates a role for regulated production of mitochondrial ROS in organismal lifespan.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  68. Yang, W. & Hekimi, S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 8, e1000556 (2010).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  69. Owusu-Ansah, E., Song, W. & Perrimon, N. Muscle mitohormesis promotes longevity via systemic repression of insulin signaling. Cell 155, 699–712 (2013).

    CAS  PubMed  Article  Google Scholar 

  70. Fiermonte, G. et al. The sequence, bacterial expression, and functional reconstitution of the rat mitochondrial dicarboxylate transporter cloned via distant homologs in yeast and Caenorhabditis elegans. J. Biol. Chem. 273, 24754–24759 (1998).

    CAS  PubMed  Article  Google Scholar 

  71. Losman, J.-A., Koivunen, P. & Kaelin, W. G. 2-Oxoglutarate-dependent dioxygenases in cancer. Nat. Rev. Cancer 20, 710–726 (2020).

    CAS  PubMed  Article  Google Scholar 

  72. Selak, M. A. et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7, 77–85 (2005). This paper illustrated the importance of SDH mutations in cance pathogenesis via accumulated succinate.

    CAS  PubMed  Article  Google Scholar 

  73. Carey, B. W., Finley, L. W., Cross, J. R., Allis, C. D. & Thompson, C. B. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518, 413–416 (2015).

    CAS  PubMed  Article  Google Scholar 

  74. Hems, R., Stubbs, M. & Krebs, H. A. Restricted permeability of rat liver for glutamate and succinate. Biochem. J. 107, 807–815 (1968).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. Ehinger, J. K. et al. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency. Nat. Commun. 7, 12317 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. MacDonald, M. J., Fahien, L. A., Mertz, R. J. & Rana, R. S. Effect of esters of succinic acid and other citric acid cycle intermediates on insulin release and inositol phosphate formation by pancreatic islets. Arch. Biochem. Biophys. 269, 400–406 (1989).

    CAS  PubMed  Article  Google Scholar 

  77. Hochachka, P. W. & Dressendorfer, R. H. Succinate accumulation in man during exercise. Eur. J. Appl. Physiol. Occup. Physiol. 35, 235–242 (1976).

    CAS  PubMed  Article  Google Scholar 

  78. Taegtmeyer, H. Metabolic responses to cardiac hypoxia. Increased production of succinate by rabbit papillary muscles. Circ. Res. 43, 808–815 (1978).

    CAS  PubMed  Article  Google Scholar 

  79. Hochachka, P. W., Owen, T. G., Allen, J. F. & Whittow, G. C. Multiple end products of anaerobiosis in diving vertebrates. Comp. Biochem. Physiol. B 50, 17–22 (1975).

    CAS  PubMed  Article  Google Scholar 

  80. Prag, H. A. et al. Mechanism of succinate efflux upon reperfusion of the ischaemic heart. Cardiovasc. Res. 117, 1188–1201 (2020).

    PubMed Central  Article  CAS  Google Scholar 

  81. Bisbach, C. M. et al. Succinate can shuttle reducing power from the hypoxic retina to the O2-rich pigment epithelium. Cell Rep. 31, 107606 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Wu, J.-Y. et al. Cancer-derived succinate promotes macrophage polarization and cancer metastasis via succinate receptor. Mol. Cell 77, 213–227.e5 (2020).

    CAS  PubMed  Article  Google Scholar 

  83. Mills, E. L. et al. UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nat. Metab. 3, 604–617 (2021).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. An, Y. A. et al. The mitochondrial dicarboxylate carrier prevents hepatic lipotoxicity by inhibiting white adipocyte lipolysis. J. Hepatol. 75, 387–399 (2021).

    CAS  PubMed  Article  Google Scholar 

  85. Andrienko, T. N., Pasdois, P., Pereira, G. C., Ovens, M. J. & Halestrap, A. P. The role of succinate and ROS in reperfusion injury—a critical appraisal. J. Mol. Cell. Cardiol. 110, 1–14 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. Bisbach, C., Hass, D. & Hurley, J. Monocarboxylate transporter 1 (MCT1) mediates succinate export in the retina. Preprint at bioRxiv https://doi.org/10.1101/2021.11.19.469314 (2021).

  87. Pajor, A. M. Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family. Pflug. Arch. 466, 119–130 (2014).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Claudia Adams Barr Program (E.T.C.), the Lavine Family Fund (E.T.C.), the Pew Charitable Trust (E.T.C.), NIH DK123095 (E.T.C.), The Smith Family Foundation (E.T.C.), Medical Research Council UK (MC_UU_00015/3) (M.P.M.) and by a Wellcome Trust Investigator award (220257/Z/20/Z) (M.P.M.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Michael P. Murphy or Edward T. Chouchani.

Ethics declarations

Competing interests

E.T.C. is a founder, board member and equity holder in Matchpoint Therapeutics. M.P.M. holds shares in Antipodean Pharmaceuticals Inc. E.T.C. and M.P.M. hold patents in the field of therapeutic modulation of succinate metabolism.

Peer review

Peer review information

Nature Chemical Biology thanks Navdeep Chandel, Luke O’Neill and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Murphy, M.P., Chouchani, E.T. Why succinate? Physiological regulation by a mitochondrial coenzyme Q sentinel. Nat Chem Biol 18, 461–469 (2022). https://doi.org/10.1038/s41589-022-01004-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-022-01004-8

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing