Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(6): 141-154

Mithochondria signaling in adaptation to hypoxia

Luk'ianova LD

    Institute of General Pathology and Pathophysiology, RAMS, Moscow, Russia
DOI: https://doi.org/10.15407/fz59.06.141

Abstract

A bioenergetic mechanism for development of urgent adaptation to hypoxia is considered. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia necessary for 1) succinate- related energy synthesis in conditions of oxygen deficiency and formation of urgent resistance in the body; 2) succinate- related stabilization of HIF-1alpha and initiation of its transcriptional activity related with formation of urgent and long-term adaptation; 3) succinate- related activation of a succinate-specific receptor GPR91. Therefore succinate is a signaling molecule, and its effects are realized at three levels in hypoxia, intramitochondrial, intracellular and intercellular.

Keywords: hypoxia, adaptation, respiratory chain reprogramming,mitochondrial complexes I and II, HIF-1б, GPR91

Full text: (PDF, in Russian)

References

  1. Kirova Yu.I., Germanova E.L., Luk'yanova L.D. Fenotipicheskie osobennosti dinamiki soderzhaniya HIF-1α v neortekse kris pri razlichnih rezhimah gipoksii . Byul. eksperim. biologii i meditsini. 2012. 154(12). P. 681-686.
    2.  
  2. Luk'yanova L.D. Bioenergeticheskaya gipoksiya. ponyatie, mehanizmi, korrektsiya . Tam zhe. 1997. 124 (9). P. 244-254.
    3.  
  3. Luk'yanova L.D. Mitohondrial'naya disfunktsiya tipovoi patologicheskii protsess, molekulyarnii mehanizm gipoksii. V kn.: Problemi gipoksii. molekulyarnie, fiziologicheskie i klinicheskie aspekti . Pod red. Luk'yanovoi L.D, Ushakova I.B. M., 2004. P. 5-31.
    4.  
  4. Luk'yanova L.D. Cignal'naya funktsiya mitohondrii pri gipoksii i adaptatsii . Patogenez. 2008, N 3. P. 4-12.
    5.  
  5. Luk'yanova L.D. Sovremennie problemi adaptatsii k gipoksii. Signal'nie mehanizmi i ih rol' v sistemnoi regulyatsii . Patol. fiziologiya i eksperim.. terapiya. 2011, N 1. P. 3-19.
    6.  
  6. Luk'yanova L.D., Germanova E.L., Tsibina T.A., Chernobaeva G.N. Energotropnoe deistvie suktsinatsoderzhashchih proizvodnih 3-oksipiridina . Byul. eksperim. biologii i meditsini. 2009. 148(10). P. 388-392.
    7.  
  7. Luk'yanova L.D, Germanova E.L., Kopaladze R.A.. Zakonomernosti formirovaniya rezistentnosti organizma pri raznih rezhimah gipoksicheskogo prekonditsionirovaniya. rol' gipoksicheskogo perioda i reoksigenatsii . Tam zhe. 2009. 147(4). P. 380-384.
    8.  
  8. Luk'yanova L.D., Dudchenko A.M., Tsibina T.A., Germanova E.L., Tkachuk E.N., Erenburg I.V. Deistvie interval'noi normobaricheskoi gipoksii na kineticheskie svoistva mitohondrial'nih fermentov . Tam zhe. 2007, N 12. P.644-651.
    9.  
  9. Luk'yanova L.D., Kirova Yu.I. Vliyanie gipoksicheskogo prekonditsionirovaniya na svobodnoradikal'nie protsessi v tkanyah kris s razlichnoi tolerantnost'yu k gipoksii . Tam zhe. 2011. 151(3). P. 263-267.
    10.  
  10. Luk'yanova L.D., Kirova Yu.I., Sukoyan G.V. Signal'nie mehanizmi adaptatsii k gipoksii i ih rol' v sistemnoi regulyatsii . Biol. membrani. 2012, N 4. P. 238-252.
    11.  
  11. Luk'yanova L.D., Sukoyan G.V, Kirova Yu. I. O roli provospalitel'nih faktorov, NO i nekotorih pokazatelei lipidnogo obmena v formirovanii srochnoi adaptatsii k gipoksii i akkumulyatsii HIF-1α . Byul. eksperim. biologii i meditsini. 2012. 11. P. 510-514.
    12.  
  12. Maevskii E.I., Rozenfel'd A.S., Grishina E.V., Kondrashova M.N. Korrektsiya metabolicheskogo atsidoza putem podderzhaniya funktsii mitohondrii. Pushchino, 2001. PubMed
    13.  
  13. Agani F. H., Pichiule P., Chavez J.C., La Manna J.C. The role of Mitochondria in the regulation of Hypoxia-inducible Factor 1 Expression during Hypoxia . JBC. 2000. 275(46). p. 35863-35867. CrossRef PubMed
    14.  
  14. Agani F. H., Puchowicz M., Chavez J.C., Pichiule P., LaManna J. Inhibitors of mitochondrial complex I attenuate the accumulation of hypoxia-inducible factor-1 during hypoxia in Hep3B cells . Compar. Biochem. and Physiol. 2000. 132(1). p. 107-109. CrossRef  
  15. Agani F.H., Pichule P., Chavez C., LaManna J.C. Inhibitors of mitochondrial complex I attenuate the accumulation of hypoxia-inducible factor-1 during hypoxia in Hep3B cells . Compar. Biochem. Physiol. Part A. 2002. 132(1). p. 107-109. CrossRef  
  16. Aithal H.N, Ramasarma T. Activation of liver succinate dehydrogenase in rats exposed to hypobaric conditions . Biochem J. 1969. 115(1). p. 77-83. CrossRef PubMed PubMedCentral
    17.  
  17. Baumbach L., Leyssac P.P., Skinner S.L. Studies on rennin release from isolated superfused glomeruli. effects of temperature, urea, oubain and ethacrynic acid . J. Physiol. 1976. 258. p. 243-256. CrossRef PubMed PubMedCentral
    18.  
  18. Baysal B.E. On the assotiation of succinate dehydrogenese mutations with hereditary paraganglion . Trends Endocrinil. Metab. 2003. 14. p. 453-459. CrossRef PubMed
    19.  
  19. Brandt U. Proton translocation by membrane-bound NADH-ubiquinone oxidoreductaise (complex I) through redox-gated ligand conduction . Biochem. Biophys. Acta. 1997. 1318. p. 79-91. CrossRef  
  20. Briere J-J., Chretien D., Benit P., Rustin P. Respiratory chain defects. what do we know for sure about their consequences in vivo . BBA. 2004. 1659. p. 172-177. CrossRef  
  21. Brunk U.T., Terman A. The mitochondrial-lysosomal axis theory of aging . Eur. J. Biochem. 2002. 269. p. 1996-2002. CrossRef PubMed
    22.  
  22. Butow R.A., Avadhani N.G. Mitochondria signaling . The retrograde response. Molecular Cell. 2004. 14(1). p. 1-15. CrossRef  
  23. Cascarano J., Ades I.Z., O'Conner J.D. Hypoxia. a succinate-fumerate electron shuttle between peripheral cells and lung . J Exp Zool. 1976. 198(2). p. 149-153. CrossRef PubMed
    24.  
  24. Chandel N.S., Schumacker P.T. Cell depleted of mitochondrial DNA (ρº) yield insight into physiological mechanisms . FEBS Lett. 1999. 454. p. 173-176. CrossRef  
  25. Chandel N.S., Schumacker P.T. Cellular oxygen sensing by mitochondria. old questions, new insight . J. Amer. Physiol. 2000. 88. p. 1880-1889. CrossRef  
  26. Chavez J.C., Agani F., Pichule P., LaManna J.C. Expression of hypoxia-inducible factor-1α in the brain of rats during chronic hypoxia . Ibid. 2000. 89(5). p. 1937- 1942. CrossRef  
  27. Correa P.R., Kruglov E.A, Thompson M., Leite M.F., Dranoff J.A., Nathanson M.H. Succinate is a paracrine signal for liver damage . J. Hepatology. 2007. 47. p. 262-269. CrossRef PubMed PubMedCentral
    28.  
  28. Das J. The role of mitochondrial respiration in physiological and evolutionary adaptation . Bioessays. 2006. 28(9). p. 890-901. CrossRef PubMed
    29.  
  29. Da Silva M.M., Sartori A., Belisle E., Kowaltowsky A.J. Ischemic preconditioning inhibits mitochondrial respiration, increase H2O2 release, and enhances K+ transport . Amer. J. Physiol. Heart Circ. Physiol. 2003. 285. P. 154-162. CrossRef PubMed
    30.  
  30. Devin A., Rigoulet M. Mechanisms of mitochondrial response to variations in energy demand in eukaryotic cells . Amer. J. Physiol. Cell Physiol. 2007. 292(1). p. 52-58. CrossRef PubMed
    31.  
  31. Di Lisa F., Ziegler M. Pathophysiological revelance of mitochondria in NAD+ metabolism . FEBS Lett. 2001. 492. p. 4-8. CrossRef  
  32. Duchen M.R. Roles of Mitochondria in Health and Disease. Diabetes. 2004. 53. p. 96-102. CrossRef  
  33. Feldkamp T., Kribben A., Roeser N.F., Senter R.A., Kemner S., Venkatachalam M.A., Nissim I., Weinberg J.M. Preservation of complex I function during hypoxiareoxygenation-induced mitochondrial injury in proximal tubules . Amer. J. Renal. Physiol. 2004. 286(4). p. 749-759.
    34.  
  34. Fiermonte G. Organization and sequence of the gene for the human mitochondrial dicarboxylate carrier. evolution of the carrier family . Bioch. J. 1999. 344. p. 953-960. CrossRef  
  35. Felty Q., Roy D. Estrogen, mitochondrea, and growth of cancer non cancer cells . J. Carcinogenesis. 2005. 4, N 1. p. 1-34. CrossRef PubMed PubMedCentral
    36.  
  36. Genova M.I., C. Casteluccio, R. Fato, G. Parenti-Castelli, M. Merlo-Pich, G. Formiggini, C. Bovina, M. Marchetti, G. Lenaz. Major changes in Complex I activity in mitochondrian from aged rats may not be detected by direct assay of NADH-coenzymeQ reductase . Biochem. J. 1995. 311. p. 105-109. CrossRef PubMed PubMedCentral
    37.  
  37. Gnaiger E. Mitochondrial Physiology. The many Faces and functions of on organelle. MiP . Austria, 2005. PubMed
    38.  
  38. Goldberg N. D., Passonneau J. V., Lowry O.H. Effects of Changes in Brain Acid Cycle Intermediates . J. Biol. Chem. 1966. 241. p. 3997-4003. PubMed
    39.  
  39. Grai M.W., Burger G., Lang B.F. Mitochondrion evolution . Science. 1999. 283. P. 1467- 1481.
    40.  
  40. Gullans, S. R., Kone, B. C., Avison, M. J., Giebisch, G. Succinate alters respiration, membrane potential, and intracellular K+ in proximal tubule . Amer. J. Physiol. 1988. 55. p. F1170-F1177.
    41.  
  41. Gutman M. Modulation of mitochondrial succinate dehydrogenese activity, mechanism and function. Mol . Cell Biochem. 1978. 20. p. 41-60. CrossRef PubMed
    42.  
  42. Hakak Y., Lehmann-Bruinsma K., Phillips Sh., Le Th., Llaw Ch., Connolly DT., Behan D.P.The role of the GPR91 ligand succinate in hematopoiesis . J. Leukoc. Boil. 2009. 85. p. 229-243. CrossRef PubMed
    43.  
  43. He W., Miao F.J., Lin D.C. Citric acid cycle intermediates as ligands for orphan-G-protein-coupled receptors . Nature. 2004. 429. p. 188-193. CrossRef PubMed
    44.  
  44. Hems, D. A., Brosnan, J. T. Effects of ischaemia on content of metabolites in rat liver and kidney in vivo . Biochem. J. 1970. 120. p. 105-111. CrossRef PubMed PubMedCentral
    45.  
  45. Hewitson K. S., Lienard B. M., McDonough M. A., Clifton I. J., Butler D., Soares A. S., Oldham N.J., McNeill L.A., Schofield C.J. Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarbonic acid cycle intermediates . J. Biol Chem. 2007. 282(5). p. 3293-3230. CrossRef PubMed
    46.  
  46. Hochachka P. W., Dressendorfer R. H. Succinate accumulation in man during exercise . Eur. J. Appl. Physiol. Occup. Physiol. 1976. 35. p. 235-242. CrossRef PubMed
    47.  
  47. Hochachka P.W., Somero G.N. Biochemical Adaptation Mechanism and Process in Physiological Evolution . New York. Oxford University Press, 2001.
    48.  
  48. Hohl C., Oestreich R., Rösen P., Wiesner R., Grieshaber M. Evidence for succinate production by reduction of fumarate during hypoxia inisolat adult rat heart cells . Arch Biochem, and Biophys. 1987. 59(2). P. 527-535. CrossRef  
  49. Kermorvant-Duchemin E., Sapieha P., Sirinyan M., Beauchamp M., Checchin D., Hardy P., Sennlaub F., Lachapelle P., Chemtob S. Understanding ischemic retinopathies. emerging concepts from oxygen-induced retinopathy . Doc Ophthalmol. 2010. 120. P. 51-60. CrossRef PubMed
    50.  
  50. Kim J-W., Tchernyshyov I., Semenza G. L., Dang C. V. HIF-1-mediated expression of pyruvate dehydrogenase kinase. A metabolic switch required for cellular adaptation to hypoxia . Cell Metabolism. 2006. 3(3). P. 150-151. CrossRef PubMed
    51.  
  51. King A., Selak M. A., Gottlieb E. Succinate dehydrogenase and fumarate hydratase. linking mitochondrial dysfunction and cancer . Oncogene. 2006. 25(34). P. 4675-4682. CrossRef PubMed
    52.  
  52. Kolvunen P., Hirsila M., Remes A.M., Hassinen I.E., Kivirikko K.I., Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydrolases by citric acid cycle intermediates. possible links between cell metabolism and stabilization of HIF. J Biol Chem. 2007. 82(7). P. 4524-4532. CrossRef PubMed
    53.  
  53. Komaromy-Hiller G., Sundquist P.D., Jacobsen L.J., Nuttall K.L. Serum succinate by capillary zone electrophoresis. marker candidate for hypoxia . Ann Clin Lab Sci. 1997. 27(2). P. 163-168. PubMed
    54.  
  54. Kondrashova M. N. The formation and utilization of succinate in mitochondria as a control mechanism of energization and energy state of tissue. In: Chance B. (Ed.). Biological and Biochemical Oscillators . New York: Acad. Press. 1993. P. 373-397.
    55.  
  55. Kondrashova M.N., Doliba N.M. Polarografiphic observation of substrate-level phosphorylation and its stimulation by acetylcholine . FEBS Lett. 1989. 243. P. 153-155. CrossRef  
  56. Kunz W.S. Kudin A.P., Vielhaber S., Blumke I. Mitochondrial complex I deficiency in epileptic focus of patients with temporal lode epilepsy . Ann. Neurol. 2000. 48. P. 766-773. CrossRef  
  57. Kushnir, M. M., Komaromy-Hiller, G., Shushan, B., Urry, F. M., Roberts, W. L. Analysis of dicarboxylic acids by tandem mass spectrometry.High-throughput quantitative measurement of methylmalonic acid in serum, plasma, and urine . Clin. Chem. 2001. . P. 1993-2002. PubMed
    58.  
  58. Kusnetsov A.V., Schneeberger S., Seiler R., Brandacher G., Mark W., Steurer W., Sacs V., Usson Y, Margreiter R, Gnaiger E. Mitochondria. defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion . Amer. J. Heart. Circ. Physiol. 2004. 286. P. H1633-H1641. CrossRef PubMed
    59.  
  59. Lukyanova L.D. Limiting steps of energy metabolism in brain in hypoxia . Neurochem. Intern. 1988. 13(I). P. 146-147.
    60.  
  60. Lukyanova L.D. Molecular, metabolic and functional mechanisms of individual resistance to hypoxia. In. Sharma B.K., Takeda N., et al. (eds), Adaptation Biology and Medicine, Narosa Publishing House New Dehli, India. 1997. I. P. 261-272. PubMed
    61.  
  61. Lukyanova L. D. Cellular mechanism responsible for beneficial effects of hypoxic therapy. In. Adaptation Biology and Medicine. Moraveč, et al. (eds), Narosa Publishing House New Dehli, India. 2002. 3. P. 290-303.
    62.  
  62. Lukyanova L.D. Novel approaches to the understanding of molecular mechanisms of adaptation. In. Adaptation Biology and Medicine. Hargens A., Takeda N., Singal P.K. (eds). 2004.4. P. 11-22. PubMed
    63.  
  63. Lukyanova L. D., A. M. Dudchenko. Regulatory role of the adenylate pool in the formation of hepatocyte resistance to hypoxia. In. K.B. Pandolf, N. Takeda, P.K. Singal (eds.), Adaptation Biology and Medicine. Narosa Publishing House New Dehli, India. 1999. 2. P. 139-150. PubMedCentral
    64.  
  64. Lukyanova L.D., Dudchenko A.V., Tsybina T.A., Germanova E.L., Tkatchuk E.N. Mitochondrial signaling in adaptation to hypoxia. In. Adaptation Biology and Medicine. Eds Lukyanova L., Singal P., Takeda N. New Dehli, India. Narosa Publ. House. 2008. 5. P. 5-15.
    65.  
  65. Lukyanova L.D., Dudchenko A.M., Germanova E.L.,Tsybina T.A.,Kapaladse R.A., Ehrenbourg I.V., Tkatchouk E.N. Mitochondria signaling in formation of body resistance to hypoxia. Intermitten Hypoxia. from molecular mechanisms to clinical applications . Eds. Lei Xi, Serebrovskaya T. Nova Science Publishers, USA Chapter. 2009. 20. P. 423-450.
    66.  
  66. Lukyanova L. D., Germanova E. L, Kirova Yu. I. The Signal Function of Succinate and Free Radicals in Mechanisms of Preconditioning and Long-termAdaptation to Hypoxia. In. Adaptation Biology and Medicine. Cell Adaptations and Challenges. Wang P., Kuo C.-H., Takeda N. and Singal P.K. (eds). 2011. 6. P. 251-277. PubMedCentral
    67.  
  67. MacDonald M.J., Fahien L.A., Brown L.J., Hasan N.M., Buss J.D., Kendrick M. A. Perspective. emerging evidence for signaling roles of mitochondrial anaplerotic products insulin secretion . Amer. J. Physiol. Endocrinol. Metab. 2005. 288. P. E1-E15. CrossRef PubMed
    68.  
  68. Maklashinas E., Sher E., Zhou H-Z, Gray M. Effect of anoxia. reperfusion on the reversible active. de-active transition of complex I in rat hear . BBA, Bioenergetics. 2002. 1556(1). P. 6-12. CrossRef  
  69. Mela L., Goodwin C.W., Miller L.D. In vivo control of mitochondrial enzyme concentrations and activity by oxygen . Amer. J. Physiol. 1976. 231. P. 1811-1816. CrossRef PubMed
    70.  
  70. Michiels K. Physiological and pathological responses to hypoxia . Amer. J. Pathology. 2004. 164. P. 1875-1882. CrossRef  
  71. Murphy E. Primary and Secondary Signaling Pathways in Early Preconditioning That Converge on the Mitochondria to Produce Cardioprotection . Circulat. Res. 2004. 94. P. 7-16. CrossRef PubMed
    72.  
  72. Napolitano M., Centoze D., Gubellini P., Rossi S., Spiezia S., Bernardi G., Gulino F., Calabresi P. Inhibition of mitochondrial complex II alters strial expression of genes involved in glutamatergi signaling. possible implications for Huginton's diease . Neurobiol. Dis. 2004. 15(2). P. 407-414. CrossRef PubMed
    73.  
  73. Nichols D.G., Samantha L.B. Mitochondria and Neuronal Survival . Physiol Rev. 2000. 80(1). P. 315-360. CrossRef PubMed
    74.  
  74. Nishimura G, Proske RJm Doyama H, Higuchi M. Regulation of apoptosis by respiratory substrates . FEBS Letters. 2001. 505, N 3. P. 399-404. CrossRef  
  75. Nowak G., Clifton G. L, Bakajsova D. Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells . J. Pharmacol. Exp Therap. 2008. 324(3). P. 1155-1162. CrossRef PubMed PubMedCentral
    76.  
  76. Paddenberg R., Ishak B., Goldenberg A., Faulhammer P., Rose F., Weissmann N., Braun Dullaeus R., Kummer W. Essential role of complex II of the respiraitory chain in hypoxia-induced ROS generation in pulmonary vasculature . Amer. J. Physiol. Lung. Cell Mol. Physiol. 2003. 284. P. 1710-1719. CrossRef PubMed
    77.  
  77. Peers Ch., Kemp P.J. Acute oxygen sensing. diverse but convergent mechanisms in airway and arterial chemoreceptors . Respirat. Res. 2001. 2(3). P. 145-149. CrossRef PubMed PubMedCentral
    78.  
  78. Peter M.T. Deen and Joris H. Robben Succinate Receptors in the Kidney . J. Amer. Soc Nephrol. 2011. 22. P. 1416-1422, CrossRef PubMed
    79.  
  79. Pitkänen S., B.H. Robinson. Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase . J. Clin. Invest. 1996. 98. P. 345-351. CrossRef PubMed PubMedCentral
    80.  
  80. Porwol T., Eheleben W., Brand V., Acker H. Tissue oxygen sensor function of NADPH oxidase isoforms, an unusiual cytochrome aa3 and reactive oxygen species . Respirat. Physiol. 2001. 128(3). P. 331-348. CrossRef  
  81. Regard J.B., Sato I.T., Coughlin S.R. Anatomical profiling of G protein-coupled receptor expression . Cell. 2008. 135. P. 561-571. CrossRef PubMed PubMedCentral
    82.  
  82. Robinson B.H. Human Comlex I deficiency. Clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect . Biochem. Biophys. Acta. 1998. 1364. P. 271-286. CrossRef  
  83. Rouslin W., Millard R.W. Canine myocardial ischemia. defect in mitochondrial electron transfer complex I. J. Mol. Cell Cardiol. 1980. 12. P. 639-645. CrossRef  
  84. Rubic T., Lametschwandtner G., Hinteregger S., Kund J. (Triggering the succinate receptor GPR91 on dendritic cells enhances immunity . Nat Immunol. 2008. 9. P. 1261-1269. CrossRef PubMed
    85.  
  85. Sadek H.A., Sweda P.A., Sweda.L.I. Modulation of mitochondrial complex I activity by reversible Ca2+ and NADH mediated superoxide anion dependent inhibition . Biochemistry. 2004. 43. P. 8494-8502. CrossRef PubMed
    86.  
  86. Sadagopan N., Roberds S.L., Major T., Preston G.M., YuY., Tones M.A. Circulating succinate is elevated in rodent models of hypertension and metabolic disease . Amer. J. Hypertens. 2007. 20. P. 1209-1215. PubMed
    87.  
  87. Sanborn T., Gavin,W., Berkowitz S., Perille T., Lesch M. Augmented conversion of aspartate and glutamate to succinate during anoxia in rabbit heart . Amer. J. Physiol. 1979. 237. P. H535-H541. PubMed
    88.  
  88. Sapieha P., Sirinyan M., Hamel D., Zaniolo K, Joya J.-S., Cho J.-H., Honoré J.-C., Kermorvant-Duchemin E., Varma D. R., Tremblay S., Leduc M., Rihakova L., Hardy P., Klein W. H., Mu X., Mamer O., Lachapelle P., Di Polo A., Beauséjour C., Andelfinger G., Mitchell G., Sennlaub F., Chemtob S., The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis . Nat. Med. 2008. 14. P. 1067-1076. CrossRef PubMed
    89.  
  89. Sardanelli A.M., Papa S. Phosphorylationof an 18 kDa subunit of bovine Heart complex I by camp dependent kinase . FEBS Lett. 1996. 379. P. 299-301. CrossRef  
  90. Sekine T., Miyazaki H., Endou H. Molekular physiology of renal organic anion transporters . Amer. J. Renal Physiol. 2006. 290. P. F251-F261. CrossRef PubMed
    91.  
  91. Selak M.A, Armour S.M., McKenzie E. D. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-prolyl hydroxylase . Cancer Cell. 2005. 7. P. 77-85. CrossRef PubMed
    92.  
  92. Semenza G.L. Signal transduction to hypoxia-inducible factor 1 . Bioch. Pharmacol. 2002. 64. P. 993-998. CrossRef  
  93. Semenza G.L. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1 . Biochem J. 2007. 405(1). P. 1-9. CrossRef PubMed
    94.  
  94. Semenza G.L. Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis . Blood. 2009. 114(10). P. 2015-2019. CrossRef PubMed
    95.  
  95. Semenza G.L., Wang G. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation . Mol.Cell Biol. 1992. 12. P. 5447-5454. CrossRef PubMed PubMedCentral
    96.  
  96. Stroka D.M., Burkhardt T., Desballerts I. HIF-1 is expressed in normoxia tissue and displays an organ-specific regulation under systemic hypoxia . FASEB J. 2001. 15. P. 2445-2453. CrossRef  
  97. Taegmeyer H. Metabolic responses to cardiac hypoxia. increased production of succinate by rabbit papillary muscles . Circ Res. 1978. 43. P. 808-815. CrossRef  
  98. Toma I., Kang J.J., Sipos A., Vargas S., Bansal E., Hanner F., Meer E., Peti-Peterdi J. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney . J. Clin. Invest. 2008. 118. P. 2526-2534. CrossRef  
  99. Wang G., Semenza G.L. Characterization of hypoxia-inducible factor I and regulation of DNA binding activity by hypoxia . J. Biol Chem; 1993. 268. P. 21513-21518. PubMed
    100.  
  100. Weinberg J.M., Venkatachalm M.A, Nancy F. Anaerobic and aerobic pathways for salvage of proximal tubules from hypoxia-induced mitochondrial injury . Amer. J. Renal. Physiol. 2000. 279. P. F927-F943.
    101.  
  101. Weinberg J.M.,Venkatachalm M.A., Nancy F. Mitochondrial disfunction during hypoxia. reoxigenation and its correction by anaerobic metabolism of citric acid cycle intermediates . PNAS. 2000. 97(3). P. 2826-2831. CrossRef PubMed
    102.  
  102. Vargas S.L., Toma I., Kang J.J., Meer E.J., Peti-Peterdi J. Activation of the succinate receptor GPR91 in macula densa cells causes renin release . J. Amer. Soc. Nephrol. 2009. 20. P. 1002-1011. CrossRef PubMed PubMedCentral
    103.  
  103. Vaux E.C., Metzen E., Yeates K.M., Ratcliffe P.J. Regulation of hypoxia-inducible factor is reserved in the absence of a functioning respiratory chain . Blood. 2001. 98. P. 296-302. CrossRef PubMed
    104.  
  104. Voos W., Rotgers K. Molecular chaperones as essential mediators of mitochondrial biogenesis . BBA. 2002. 1592. P. 51-62. CrossRef  
  105. Zoccarato F., Cavallini L., Bortolami S., Alexandre A. Succinate modulation of H2O2 release at NADH.ubiquinone oxidoreductase (Complex I) in brain mitochondria . Biochem J. 2007. 406(1). P.125-129. CrossRef PubMed PubMedCentral
    106.  
  106. Zhu H., Bunn F. Oxygen sensing and signaling. impact on regulation of physiologically important genes . Respir Physiol. 1999. 2. P. 239-247. CrossRef  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.