Abstract
The mitochondrial structure and the contents of subunits (NDUFV2, SDHA, Cyt b, COX1) of mitochondrial respiratory complexes I–IV as well as of the hypoxia-inducible factor (HIF-1α) in the brain cortex (BC) of rats with high resistance (HR) and low resistance (LR) to hypoxia were studied for the first time depending on the severity of hypoxia. Different regimes of 30-min hypobaric hypoxia (pO2 14, 10, and 8%) were used. It was found that cortical mitochondria responded to 30-min hypobaric hypoxia of different severity with typical and progressing changes in mitochondrial structure and function of mitochondrial enzymes. Under 14 and 10% hypoxia, animals developed compensatory structural and metabolic responses aimed at supporting the cell energy homeostasis. Consequently, these hypoxia regimes can be used for treatment in pressure chambers. At the same time, decreasing the oxygen concentration in the inhaled air to 8% led to the appearance of destructive processes in brain mitochondria. The features of mitochondrial ultrastructure and the function of respiratory enzymes in the BC of HR and LR rats exposed to normoxic and hypoxic conditions suggest that the two types of animals had two essentially distinct functional and metabolic patterns determined by different efficiency of the energy apparatus. The development of adaptive and destructive responses involved different metabolic pathways of the oxidation of energy substrates and different efficiency of the functioning of mitochondrial respiratory carriers.
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Abbreviations
- BC:
-
brain cortex
- HBH:
-
acute hypobaric hypoxia
- LR:
-
low-resistance rats
- HR:
-
high-resistance rats
- MC:
-
mitochondrial enzyme catalytic subunits
- NDUFV2:
-
NADH dehydrogenase [ubiquinone] flavoprotein 2
- SDHA:
-
flavochrome subunit A of succinate dehydrogenase
- COX1:
-
cytochrome c oxidase subunit
- HIF-1α:
-
hypoxia-inducible factor 1 alpha subunit
- RDU:
-
relative densitometric units
References
Angelova PR, Abramov AY (2018) Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett 592(5):692–702. https://doi.org/10.1002/1873-3468.12964
Appaix F, Kuznetsov AV, Usson Y, Kay L, Andrienko T, Olivares J, Kaambre T, Sikk P, Margreiter R, Saks V (2003) Possible role of cytoskeleton in intracellular arrangement and regulation of mitochondria. Exp Physiol 88:175–190. https://doi.org/10.1113/eph8802511
Berezovsky (1978) In: Berezovsky (ed) Hypoxia: individual sensitivity and reactivity. Naukova Dumka, Kiev
Chan DC (2006) Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22(310):79–99. https://doi.org/10.1146/annurev.cellbio.22.010305.104638
Chen H, Chan DC (2009) Mitochondrial dynamics–fusion, fission, movement and mitophagy in neurodegenerative diseases. Hum Mo Genet 18:R169–R176. https://doi.org/10.1093/hmg/ddp326
Chen HA, Chomyn A, Chan DC (2005) Disruption of fusion resulting mitochondrial heterogeneity and dysfunction. J Biol Chem 280(28):26185–26192
Chen TT, Maevsky EI, Uchitel ML (2015) Maintenance of homeostasis in the aging hypothalamus: the central and peripheral roles of succinate. Front Endocrinol 6(7):1–11. https://doi.org/10.3389/fendo.2015.00007
Chilov D, Camenisch G, Kvietikova I, Ziegler U, Gassmann M, Wenger RH (1999) Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1a. J Cell Sci 11:1203–1212 WOS:000080141300009
Dayala D, Martin SM, Owens KM, Aykin-Burns N, Zhu Y, Boominathan A, Pain D, Limoli CL, Goswami PC, Domann FE, Spitz DR (2009) Mitochondrial complex II dysfunction can contribute significantly to genomic instability after exposure to ionizing radiation. Radiat Res 172(6):737–745. https://doi.org/10.1667/RR1617.1
Devin A, Rigoulet M (2007) Mechanisms of mitochondrial response to variations in energy demand in eukaryotic cells. Am J Physiol Cell Physiol 292(1):52–58. https://doi.org/10.1152/ajpcell.00208.2006
Duchen MR (2004) Roles of mitochondria in health and disease. Diabetes 53(1):S96–S10. https://doi.org/10.2337/diabetes.53.2007.S96
Dudchenko A, Lukyanova LD (1996) Effects of adaptation to periodic hypoxia on kinetic parameters of respiratory chain enzymes in rat brain. Bull Exp Biol Med 121(3):232–235. https://doi.org/10.1007/BF02446754
Dudchenko AM, Chernobaeva GN, Belousova VV, Vlasova IG, Lukyanova LD (1993) Bioenergetic parameters of the brain in rats with different resistance to hypoxia. Bull Exp Biol Med 115(3):263–267. https://doi.org/10.1007/BF00836406
Feldkamp T, Kribben A, Roeser N, Senter R, Kemner S, Venkatachalam M, Nissim I, Weinberg JM (2004) Preservation of complex I function during hypoxia- reoxygenation-induced mitochondrial injury in proximal tubules. Am J Physiol Ren Physiol 286(4):F749–F759. https://doi.org/10.1152/ajprenal.00276.2003
Gomes LC, Scorrano L (2013) Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta 1833:205–212. https://doi.org/10.1016/j.bbamcr.2012.02.012
Hackenbrock CR (1966) Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J Cell Biol 30(2):269–297. https://doi.org/10.1083/jcb.30.2.269
Hackenbrock CR (1968) Ultrastructural bases for metabolically linked mechanical activity in mitochondria. II. Electron transport-linked ultrastructural transformations in mitochondria. J Cell Biol 37(2):345–369. https://doi.org/10.1083/jcb.37.2.345
Hochachka PW, Somero GN (2002) Biochemical adaptation - mechanism and process in physiological evolution. Oxford University Press, New York, p 480
Kaasik A, Veksler V, Boehm E, Novotova M, Minajeva A, Ventura-Clapier R (2001) Energetic crosstalk between organelles: architectural integration of energy production and utilization. Circ Res 89:153–159. https://doi.org/10.1161/hh1401.093440
Karbowsky M, Yorele RJ (2003) Dynamics of mitochondrial morphology in healthy cells and during apoptosis. Cell Death Differ 10(8):870–880. https://doi.org/10.1038/sj.cdd.4401260
Kondrashova MN (1993) 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. Acad. Press. New York. p. 373–397
Kondrashova MN, Zakharchenko M, Khunderyakova N (2009) Preservation of the in vivo state of mitochondrial network for ex vivo physiological study of mitochondria. Int J Biochem Cell Biol 41:2036–2050
Livanova LM, Sarkisova KY, Lukyanova LD, Kolomeitseva IA (1992) Respiration and oxidative phosphorylation of the mitochondria of the brain of rats with various types of behavior. Neurosci Behav Physiol 22(6):519–525
Lukyanova LD (2013) Mitochondrial signaling in hypoxia. OJEMD 3:20–32. https://doi.org/10.4236/ojemd.2013.32A004
Lukyanova LD, Kirova YI (2015) Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci 9:1–15. https://doi.org/10.3389/fnins.2015.00320
Lukyanova LD, Chernobaeva GN, Romanova VE (1995) Effects of adaptation to intermittent hypoxia on oxidative phosphorylation in brain mitochondria of rats with different sensitivities toward oxygen deficiency. Bull Exp Biol Med 12:1189–1192. https://doi.org/10.1007/BF02445567
Lukyanova LD, Germanova EL, Kopaladze RA (2009a) Development of resistance of an organism under various conditions of hypoxic preconditioning: role of the hypoxic period and reoxygenation. Bull Exp Biol Med 147(4):400–404. https://doi.org/10.1007/s10517-009-0529-8
Lukyanova LD, Dudchenko AM, Germanova EL, Tsybina TA, Kapaladse RA, Ehrenbourg IV, Tkatchouk EN (2009b) In: Xi L, Serebrovskaya T (eds) Intermitten hypoxia: from molecular mechanisms to clinical applications. Nova Science, USA, pp 423–450
Maciejczyk M, Mikoluc B, Pietrucha B, Heropolitanska-Pliszka E, Pac M, Motkowski R, Car H (2017) Oxidative stress, mitochondrial abnormalities and antioxidant defense in ataxia-telangiectasia, bloom syndrome and Nijmegen breakage syndrome. Redox Biol 11:375–383
Maklashinas E, Sher E, Zhou H-Z, Gray M (2002) Effect of anoxia/reperfusion on the reversible active/de-active transition of complex I in rat hear. BBA-Bioenergetics 1556(1):6–12. https://doi.org/10.1016/S0005-2728(02)00280-3
Mcillwain H, Rodnight R (1962) Practical neurochemistry. - London: J. & A. Churchill. p. 210
Mironova GD, Shigaeva MI, Gritsenko EN, Murzaeva SV, Gorbacheva OS, Germanova EL, Lukyanova LD (2010) Functioning of the mitochondrial ATP-dependent potassium channel in rats varying in their resistance to hypoxia. Involvement of the channel in the process of animal’s adaptation to hypoxia. J Bioenerg Biomembr 42(6):473–481
Nowak G, Clifton G, Bakajsova D (2008) Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells. J Pharmacol Exp Ther 324(3):1155–1162
Rana A, Oliveira MP, Khamoui AV, Aparicio R, Rera M, Rossiter HB, Walker DW (2017) Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster. Nat Commun 8(1):448. https://doi.org/10.1038/s41467-017-00525-4
Rybakova A, Makarova M (2015) Methods of euthanasia of laboratory animals, in accordance with European directive 2010/63. International Bulletin of Veterinary 2:96–104
Shutt T, Geoffrion M, Milne R, McBride HM (2012) The intracellular redox state is a key determinant of mitochondrial fusion. EMBO Rep 10:909–915. https://doi.org/10.1038/embor.2012.128
Singer TP, Kearney EB (1957) Methods of biochemical analysis. New York: Interscience, V. 4. p. 312
Starkov AA, Fiskum G (2003) Regulation of brain mitochondrial H2O2 production by membrane potential and NAD(P)H redox state. J Neurochem 86:1101–1107
Tondera D, Grandemange S, Jourdain A, Karbowski M, Mattenberger Y, Herzig S, Da Cruz S, Clerc P, Raschke I, Merkwirth C, Ehses S, Krause F, Chan DC, Alexander C, Bauer C, Youle R, Langer T, Martinou JC (2009) SLP-2 is required for stress–induced mitochondrial hyperfusion. EMBO J 28(11):1589–1600. https://doi.org/10.1038/emboj.2009.89
Van der Bliek AM, Shen Q, Kawajiri S (2013) Mechanisms of mitochondrial fission and fusion. Cold Spring Harb Perspect Biol 5(6):1–16. https://doi.org/10.1101/cshperspect.a011072
Vik SB, Hatefi Y (1981) Possible occurrence and role of an essential histidyl residue in succinate dehydrogenase (active site/mechanisms of succinate oxidation and fumarate reduction). Proc Natl Acad Sci U S A 78(11):6749–6753. https://doi.org/10.1073/pnas.78.11.6749
Weakley BS (1972) A beginners handbook in biological electron microscopy. Churchill Livingstone. Edinburg and London. 228 р. ISBN-10: 9780443009082
Wheaton W, Chandel N (2011) Hypoxia. 2. Hypoxia regulates cellular metabolism. Am J Physiol Cell Physiol 300(3):C385–C393. https://doi.org/10.1152/ajpcell.00485.2010
Acknowledgements
The work was supported by the Russian Science Foundation (RSF) (project No. 16-15-00157 to G.D.). The procedure of animal treatment and the work of technicians were supported by the Russian Foundation for Basic Research (RFBR) (project No. 18-34-00297mol_a to N.B.).
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Mironova, G.D., Pavlik, L.L., Kirova, Y.I. et al. Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage. J Bioenerg Biomembr 51, 329–340 (2019). https://doi.org/10.1007/s10863-019-09806-7
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DOI: https://doi.org/10.1007/s10863-019-09806-7