Abstract
The article considers the comparative analysis of the functional activity of mitochondria isolated from the liver of grass snakes, Natrix natrix (Linnaeus, 1758) that were kept at different temperatures (23–26 °C and 4-5 °C). It was found that liver mitochondria of hypothermia-exposed grass snakes are characterized by weak coupling of oxidative phosphorylation as compared to mitochondria of active animals which is caused by inhibition of succinate-fuelled respiration in ADP-stimulated state, as well as by activation of basal non-phosphorylating rate. Inhibition of mitochondrial respiration in hibernating animals is associated with a decrease in the activity of the respiratory chain complexes of organelles. A significant decrease in the rate of K+ transport in the liver mitochondria of hibernating animals has been established. Under these conditions, a decrease in the calcium capacity of the organelles was also revealed, which indicates a decrease in the resistance of the mitochondria of hibernating animals to the induction of the Ca2+-dependent mitochondrial pore. All these changes in the functional activity of mitochondria are observed on the background of increasing H2O2 production as well as increasing the proportion of polyunsaturated fatty acids in phospholipid composition of mitochondrial membranes, which are the targets of reactive oxygen species. It can lead to increased formation of lipid peroxides and activation of destructive processes associated with the induction of Ca2+-dependent mitochondrial pore.
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Abbreviations
- CsA:
-
cyclosporin A
- DNP:
-
2,4-dinitrophenol
- MCU:
-
mitochondrial calcium uniporter
- MPT:
-
mitochondrial permeability transition
- ROS:
-
reactive oxygen species
References
Akopova OV (2018) Some aspects of the mitochondrial KATP channel functioning under hypoxia. Biochem Physiol 7:236. https://doi.org/10.4172/2168-9652.1000236
Aloia R (1980) The role of membrane fatty acids in mammalian hibernation. Fed Proc 39:2974–2979
Andrews M (2004) Genes controlling the metabolic switch in hibernating mammals. Biochem Soc Trans 32:1021–1024. https://doi.org/10.1042/BST0321021
Andrews MT (2019) Molecular interactions underpinning the phenotype of hibernation in mammals. J Exp Biol 222(Pt 2):jeb160606. https://doi.org/10.1242/jeb.160606
Armstrong C, Staples JF (2010) The role of succinate dehydrogenase and oxaloacetate in metabolic suppression during hibernation and arousal. J Comp Physiol B 180 (5):775–783
Ballinger M, Schwartz C, Andrews M (2017) Enhanced oxidative capacity of ground squirrel brain mitochondria during hibernation. Am J Physiol Regul Integr Comp Physiol 312:R301–R310. https://doi.org/10.1152/ajpregu.00314.2016
Baranova O, Skarga Y, Negoda A, Mironova G (2000) Inhibition of 2,4-dinitrophenol-induced potassium efflux by adenine nucleotides in mitochondria. Biochemistry (Mosc) 65:218–222
Barger J, Brand M, Barners B, Boyer B (2003) Tissue specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels. Am J Phys 284:R1306–R1313. https://doi.org/10.1152/ajpregu.00579.2002
Bligh E, Dyer W (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917. https://doi.org/10.1139/o59-099
Boutilier R (2001) Mechanisms of cell survival in hypoxia and hypothermia. J Exp Biol 204:3171–3181
Boutilier RG, St-Pierre J (2002) Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression. J Exp Biol 205(Pt 15):2287–2296
Brierley G, Yung D (1980) Inhibitors of mitochondrial cations transport. Pharm Ther 8:193–216. https://doi.org/10.1016/0163-7258(80)90065-0
Brown J, Chung D, Belgrave K, Staples J (2012) Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels. Am J Phys 302:15–28. https://doi.org/10.1152/ajpregu.00230.2011
Brustovetsky N, Amerkhanov Z, Popova E, Konstantinov A (1990) Reversible inhibition of electron transfer in the ubiquinol. Cytochrome c reductase segment of the mitochondrial respiratory chain in hibernating ground squirrels. FEBS Lett 263:73–76. https://doi.org/10.1016/0014-5793(90)80708-Q
Brustovetsky NN, Egorova MV, Grishina EV, Mayevsky EI (1992) Analysis of the causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers, Citellus undulatus. Comp Biochem Physiol B 103:755–758
Carey H, Andrews M, Martin S (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181. https://doi.org/10.1152/physrev.00008.2003
Chance B, Williams G (1955) Respiratory enzymes in oxidative phosphorylation: III. The steady state. J Biol Chem 217:409–427
Chung D, Lloyd G, Thomas R, Guglielmo C, Staples J (2011) Mitochondrial respiration and succinate dehydrogenase are suppressed early during entrance into a hibernation bout, but membrane remodeling is only transient. J Comp Physiol B 181:699–711. https://doi.org/10.1007/s00360-010-0547-x
D'Alessandro A, Nemkov T, Bogren LK, Martin SL, Hansen KC (2017) Comfortably numb and back: plasma metabolomics reveals biochemical adaptations in the hibernating 13-lined ground squirrel. J Proteome Res 16:958–969. https://doi.org/10.1021/acs.jproteome.6b00884
Dubinin M, Vedernikov A, Khoroshavina E, Adakeeva S, Samartsev V (2016) Induction of calcium-dependent nonspecific permeability of the inner membrane in liver mitochondria of mammals and birds: a comparative study. Biochem (Mosc) Suppl Ser A Membr Cell Biol 10:19–27. https://doi.org/10.1134/S1990747815050037
Dubinin M, Vedernikov A, Khoroshavina E, Smirnova A, Samartsev V (2017) A comparative study of potassium ion transport in liver mitochondria of laboratory rats, pigeons (Columba livia) and guineafowl (Numida meleagris). J Evol Biochem Physiol 53:343–345. https://doi.org/10.1134/S0022093017040123
Dubinin M, Samartsev V, Stepanova A, Khoroshavina E, Penkov N, Yashin V, Starinets V, Mikheeva I, Gudkov S, Belosludtsev K (2018) Membranotropic effects of ω-hydroxypalmitic acid and Ca2+ on rat liver mitochondria and lecithin liposomes. Aggregation and membrane permeabilization. J Bioenerg Biomembr 50:391–401. https://doi.org/10.1007/s10863-018-9771-y
Fedotcheva N, Sharyshev A, Mironova G, Kondrashova M (1985) Inhibition of succinate oxidation and K+ transport in mitochondria during hibernation. Comp Biochem Physiol B 82:191–195. https://doi.org/10.1016/0305-0491(85)90151-8
Galli GLJ, Lau GY, Richards JG (2013) Beating oxygen: chronic anoxia exposure reduces mitochondrial F1FO-ATPase activity in turtle (Trachemys scripta) heart. J Exp Biol 216:3283–3293. https://doi.org/10.1242/jeb.087155
Geiser F (2004) Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239–274. https://doi.org/10.1146/annurev.physiol.66.032102.115105
Gellerich F, Trumbeckaite S, Müller T, Deschauer M, Chen Y, Gizatullina Z, Zierz S (2004) Energetic depression caused by mitochondrial dysfunction. Mol Cell Biochem 256(257):391–405. https://doi.org/10.1023/B:MCBI.0000009885.34498.e6
Hadj-Moussa H, Green SR, Storey KB (2018) The living dead: mitochondria and metabolic arrest. IUBMB Life 70:1260–1266. https://doi.org/10.1002/iub.1910
Ivanov K (2008) Life under minimal energy expenses. Usp Fiziol Nauk 39(1):42–54
Komelina NP, Polskaya AI, Amerkhanov ZG (2015) Artificial hypothermia in rats, unlike natural hibernation in ground squirrels Spermophilus undulatus, is not accompanied by the inhibition of respiration in liver mitochondria. Biochem (Mosc) Suppl Ser A Membr Cell Biol 9:293–302. https://doi.org/10.1134/S1990747815050062
Lutz P, Nilsson G (1997) Contrasting strategies for anoxic brain survival–glycolysis up or down. J Exp Biol 200:411–419
Lyons P, Lang-Ouellette D, Morin P (2013) CryomiRs: towards the identification of a cold-associated family of microRNAs. Comp Biochem Physiol D 8:358–364. https://doi.org/10.1016/j.cbd.2013.10.001
MacDonald J, Storey K (1999) Regulation of ground squirrel Na+K+-ATPase activity by reversible phosphorylation during hibernation. Biochem Biophys Res Commun 254:424–429. https://doi.org/10.1006/bbrc.1998.9960
Malysheva IN, Storey KB, Lopina OD, Rubtsov AM (2001) Ca-ATPase activity and protein composition of sarcoplasmic reticulum membranes isolated from skeletal muscles of typical hibernator, the ground squirrel Spermophilus undulatus. Biosci Rep 21:831–838. https://doi.org/10.1023/A:1015540909212
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 42:473–481. https://doi.org/10.1007/s10863-010-9316-5
Muleme H, Walpole A, Staples J (2006) Mitochondrial metabolism in hibernation: metabolic suppression, temperature effects, and substrate preferences. Physiol Biochem Zool 79:474–483. https://doi.org/10.1086/501053
Munro D, Thomas DW (2004) The role of polyunsaturated fatty acids in the expression of torpor by mammals: a review. Zoology 107 (1):29–48
Pamenter ME, Gomez CR, Richards JG, Milsom WK (2016) Mitochondrial responses to prolonged anoxia in brain of red-eared slider turtles. Biol Lett 12:20150797. https://doi.org/10.1098/rsbl.2015.0797
Rasola A, Bernardi P (2011) Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium 50:222–233. https://doi.org/10.1016/j.ceca.2011.04.007
Rauen U, de Groot H (2004) New insights into the cellular and molecular mechanisms of cold storage injury. J Investig Med 52:299–309. https://doi.org/10.1136/jim-52-05-29
Ruf T, Arnold W (2008) Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis. Am J Physiol Regul Integr Comp Physiol 294:R1044–R1052. https://doi.org/10.1152/ajpregu.00688.2007
Samartsev V (2000) Fatty acids as uncouplers of oxidative phosphorylation. Biochemistry (Mosc) 65:991–1005
Samartsev V, Smirnov A, Zeldi I, Markova O, Mokhova E, Skulachev V (1997) Involvement of aspartate/glutamate antiporter in fatty acid-induced uncoupling of liver mitochondria. Biochim Biophys Acta 1319:251–257. https://doi.org/10.1016/S0005-2728(96)00166-1
Savina M, Emelyanova L, Brailovskaia I (2009) Bioenergetics of the lower vertebrates. Mechanisms of adaptations to anoxia and hypoxia. J Evol Biochem Physiol 45:197–210. https://doi.org/10.1134/S0022093009020029
Schönfeld P, Wojtczak L (2007) Fatty acids decrease mitochondrial generation of reactive oxygen species at the reverse electron transport but increase it at the forward transport. Biochim Biophys Acta 1767:1032–1040. https://doi.org/10.1016/j.bbabio.2007.04.005
Schönfeld P, Wojtczak L (2008) Fatty acids as modulators of the cellular production of reactive oxygen species. Free Radic Biol Med 45:231–241. https://doi.org/10.1016/j.freeradbiomed.2008.04.029
Skoczylas R (1970) Influence of temperature on gastric digestion in the grass snake, Natrix natrix L. Comp Biochem Physiol 33:793–796. https://doi.org/10.1016/0010-406X(70)90028-9
Spinazzi M, Casarin A, Pertegato V, Salviati L, Angelini C (2012) Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc 7:1235–1246. https://doi.org/10.1038/nprot.2012.058
Staples JF (2016) Metabolic flexibility: hibernation, torpor, and estivation. Compr Physiol 6:737–771. https://doi.org/10.1002/cphy.c140064
Storey K, Storey J (2004) Metabolic rate depression in animals: transcriptional and translational controls. Biol Rev Camb Philos Soc 79:207–233. https://doi.org/10.1017/S1464793103006195
Storey K, Storey J (2010) Metabolic rate depression: the biochemistry of mammalian hibernation. Adv Clin Chem 52:77–108. https://doi.org/10.1016/S0065-2423(10)52003-1
St-Pierre J, Brand MD, Boutilier RG (2000) Mitochondria as ATP consumers: cellular treason in anoxia. PNAS 97:8670–8674. https://doi.org/10.1073/pnas.140093597
van Breukelen F, Martin S (2002) Reversible depression of transcription during hibernation. J Comp Physiol B 172:355–361. https://doi.org/10.1007/s00360-002-0256-1
Williams CT, Goropashnaya AV, Buck CL, Fedorov VB, Kohl F, Lee TN, Barnes BM (2011) Hibernating above the permafrost: effects of ambient temperature and season on expression of metabolic genes in liver and brown adipose tissue of arctic ground squirrels. J Exp Biol 214:1300–1306. https://doi.org/10.1242/jeb.052159
Zavodnik I, Dremza I, Cheshchevik V, Lapshina E, Zamaraewa M (2013) Oxidative damage of rat liver mitochondria during exposure to t-butyl hydroperoxide. Role of Ca2+ ions in oxidative processes. Life Sci 92:1110–1117. https://doi.org/10.1016/j.lfs.2013.04.009
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The work was supported by grant from the Russian Foundation for Basic Research (18-315-00033) and the Ministry for Education and Science of the Russian Federation (state commissions no. 6.5170.2017/8.9 and 17.4999.2017/8.9).
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Dubinin, M.V., Svinin, A.O., Vedernikov, A.A. et al. Effect of hypothermia on the functional activity of liver mitochondria of grass snake (Natrix natrix): inhibition of succinate-fueled respiration and K+ transport, ROS-induced activation of mitochondrial permeability transition. J Bioenerg Biomembr 51, 219–229 (2019). https://doi.org/10.1007/s10863-019-09796-6
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DOI: https://doi.org/10.1007/s10863-019-09796-6