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09.05.2024 | Original Contribution

Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43^{Cre−ER(T)/fl} mice by altering the coenzyme Q pool

verfasst von: Marta Consegal, Elisabet Miró-Casas, Ignasi Barba, Marisol Ruiz-Meana, Javier Inserte, Begoña Benito, Cristina Rodríguez, Freddy G. Ganse, Laura Rubio-Unguetti, Carmen Llorens-Cebrià, Ignacio Ferreira-González, Antonio Rodríguez-Sinovas

Erschienen in: Basic Research in Cardiology

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Abstract

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43^{Cre−ER(T)/fl} mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43^fl/fl mice and Cx43^{Cre−ER(T)/fl} knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia–reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165 ± 0.338 vs. 4.18 ± 0.55 nmol/mg protein, p < 0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43^{Cre−ER(T)/fl} mice treated with 4OHT had a smaller infarct size after IR compared to Cx43^fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate.

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Alam MS (2018) Proximity ligation assay (PLA). Curr Protoc Immunol 123:e58. https://doi.org/10.1002/cpim.58CrossRefPubMedPubMedCentral

Anastacio MM, Kanter EM, Makepeace C, Keith AD, Zhang H, Schuessler RB, Nichols CG, Lawton JS (2013) Cardioprotective mechanism of diazoxide involves the inhibition of succinate dehydrogenase. Ann Thorac Surg 95:2042–2050. https://doi.org/10.1016/j.athoracsur.2013.03.035CrossRefPubMedPubMedCentral

Arroyo A, Kagan VE, Tyurin VA, Burgess JR, de Cabo R, Navas P, Villalba JM (2000) NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane. Antioxid Redox Signal 2:251–262. https://doi.org/10.1089/ars.2000.2.2-251CrossRefPubMed

Awad K, Sayed A, Banach M (2022) Coenzyme Q10 reduces infarct size in animal models of myocardial ischemia-reperfusion injury: a meta-analysis and summary of underlying mechanisms. Front Cardiovasc Med 9:857364. https://doi.org/10.3389/fcvm.2022.857364CrossRefPubMedPubMedCentral

Basheer WA, Fu Y, Shimura D, Xiao S, Agvanian S, Hernandez DM, Hitzeman TC, Hong T, Shaw RM (2018) Stress response protein GJA1-20k promotes mitochondrial biogenesis, metabolic quiescence, and cardioprotection against ischemia/reperfusion injury. JCI Insight 3. https://doi.org/10.1172/jci.insight.121900

Boengler K, Dodoni G, Rodriguez-Sinovas A, Cabestrero A, Ruiz-Meana M, Gres P, Konietzka I, Lopez-Iglesias C, Garcia-Dorado D, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244. https://doi.org/10.1016/j.cardiores.2005.04.014CrossRefPubMed

Boengler K, Heusch G, Schulz R (2006) Connexin 43 and ischemic preconditioning: effects of age and disease. Exp Gerontol 41:485–488. https://doi.org/10.1016/j.exger.2006.01.011CrossRefPubMed

Boengler K, Konietzka I, Buechert A, Heinen Y, Garcia-Dorado D, Heusch G, Schulz R (2007) Loss of ischemic preconditioning’s cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. Am J Physiol Heart Circ Physiol 292:H1764–H1769. https://doi.org/10.1152/ajpheart.01071.2006CrossRefPubMed

Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R (2012) Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption. J Cell Mol Med 16:1649–1655. https://doi.org/10.1111/j.1582-4934.2011.01516.xCrossRefPubMedPubMedCentral

10.

Boengler K, Stahlhofen S, van de Sand A, Gres P, Ruiz-Meana M, Garcia-Dorado D, Heusch G, Schulz R (2009) Presence of connexin 43 in subsarcolemmal, but not in interfibrillar cardiomyocyte mitochondria. Basic Res Cardiol 104:141–147. https://doi.org/10.1007/s00395-009-0007-5CrossRefPubMed

11.

Boengler K, Ungefug E, Heusch G, Leybaert L, Schulz R (2013) Connexin 43 impacts on mitochondrial potassium uptake. Front Pharmacol 4:73. https://doi.org/10.3389/fphar.2013.00073CrossRefPubMedPubMedCentral

12.

Bou-Teen D, Fernandez-Sanz C, Miro-Casas E, Nichtova Z, Bonzon-Kulichenko E, Casós K, Inserte J, Rodriguez-Sinovas A, Benito B, Sheu SS, Vázquez J, Ferreira-González I, Ruiz-Meana M (2022) Defective dimerization of FoF1-ATP synthase secondary to glycation favors mitochondrial energy deficiency in cardiomyocytes during aging. Aging Cell 21:e13564. https://doi.org/10.1111/acel.13564CrossRefPubMedPubMedCentral

13.

Burger N, Logan A, Prime TA, Mottahedin A, Caldwell ST, Krieg T, Hartley RC, James AM, Murphy MP (2020) A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo. Free Radic Biol Med 147:37–47. https://doi.org/10.1016/j.freeradbiomed.2019.11.028CrossRefPubMedPubMedCentral

14.

Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. Circ Res 114:524–537. https://doi.org/10.1161/CIRCRESAHA.114.300559CrossRefPubMedPubMedCentral

15.

Chouchani ET, Pell VR, Gaude E, Aksentijevic D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord EN, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa AS, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515:431–435. https://doi.org/10.1038/nature13909CrossRefPubMedPubMedCentral

16.

Depre C, Vatner SF (2007) Cardioprotection in stunned and hibernating myocardium. Heart Fail Rev 12:307–317. https://doi.org/10.1007/s10741-007-9040-3CrossRefPubMed

17.

Diez ER, Sanchez JA, Prado NJ, Ponce Zumino AZ, Garcia-Dorado D, Miatello RM, Rodriguez-Sinovas A (2019) Ischemic postconditioning reduces reperfusion arrhythmias by adenosine receptors and protein kinase C activation but is independent of K(ATP) channels or connexin 43. Int J Mol Sci 20:5927. https://doi.org/10.3390/ijms20235927CrossRefPubMedPubMedCentral

18.

Fernandez-Sanz C, Ruiz-Meana M, Castellano J, Miro-Casas E, Nunez E, Inserte J, Vazquez J, Garcia-Dorado D (2015) Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes. Thromb Haemost 113. https://doi.org/10.1160/TH14-10-0901

19.

Gadicherla AK, Wang N, Bulic M, Agullo-Pascual E, Lissoni A, De Smet M, Delmar M, Bultynck G, Krysko DV, Camara A, Schluter KD, Schulz R, Kwok WM, Leybaert L (2017) Mitochondrial Cx43 hemichannels contribute to mitochondrial calcium entry and cell death in the heart. Basic Res Cardiol 112:27. https://doi.org/10.1007/s00395-017-0618-1CrossRefPubMed

20.

Garcia-Dorado D, Rodriguez-Sinovas A, Ruiz-Meana M (2004) Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion. Cardiovasc Res 61:386–401. https://doi.org/10.1016/j.cardiores.2003.11.039CrossRefPubMed

21.

Garcia-Dorado D, Ruiz-Meana M, Inserte J, Rodriguez-Sinovas A, Piper HM (2012) Calcium-mediated cell death during myocardial reperfusion. Cardiovasc Res 94:168–180. https://doi.org/10.1093/cvr/cvs116CrossRefPubMed

22.

Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551. https://doi.org/10.1016/j.redox.2015.08.020CrossRefPubMedPubMedCentral

23.

Halestrap AP, Richardson AP (2015) The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury. J Mol Cell Cardiol 78:129–141. https://doi.org/10.1016/j.yjmcc.2014.08.018CrossRefPubMed

24.

Hano O, Thompson-Gorman SL, Zweier JL, Lakatta EG (1994) Coenzyme Q10 enhances cardiac functional and metabolic recovery and reduces Ca2+ overload during postischemic reperfusion. Am J Physiol 266:H2174-2181. https://doi.org/10.1152/ajpheart.1994.266.6.H2174CrossRefPubMed

25.

Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, Garcia-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586. https://doi.org/10.1161/01.RES.0000181171.65293.65CrossRefPubMed

26.

Heusch G, Buchert A, Feldhaus S, Schulz R (2006) No loss of cardioprotection by postconditioning in connexin 43-deficient mice. Basic Res Cardiol 101:354–356. https://doi.org/10.1007/ss00395-006-0589-0CrossRefPubMed

27.

Heusch G, Andreadou I, Bell R, Bertero E, Botker H-E, Davidson SM, Downey J, Eaton P, Ferdinandy P, Gersh BJ, Giacca M, Hausenloy DJ, Ibanez B, Krieg T, Maack C, Schulz R, Sellke F, Shah AM, Thiele H, Yellon DM, Di Lisa F (2023) Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection. Redox Biol 67:102894. https://doi.org/10.1016/j.redox.2023.102894CrossRefPubMedPubMedCentral

28.

Hirschhauser C, Lissoni A, Gorge PM, Lampe PD, Heger J, Schluter KD, Leybaert L, Schulz R, Boengler K (2021) Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning. Basic Res Cardiol 116:21. https://doi.org/10.1007/s00395-021-00861-zCrossRefPubMedPubMedCentral

29.

Holmstrom KM, Finkel T (2014) Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 15:411–421. https://doi.org/10.1038/nrm3801CrossRefPubMed

30.

Jarmuszkiewicz W, Dominiak K, Galganski L, Galganska H, Kicinska A, Majerczak J, Zoladz JA (2020) Lung mitochondria adaptation to endurance training in rats. Free Radic Biol Med 161:163–174. https://doi.org/10.1016/j.freeradbiomed.2020.10.011CrossRefPubMed

31.

Kelly RF, Sluiter W, McFalls EO (2008) Hibernating myocardium: is the program to survive a pathway to failure? Circ Res 102:3–5. https://doi.org/10.1161/CIRCRESAHA.107.168278CrossRefPubMed

32.

Kula-Alwar D, Prag HA, Krieg T (2019) Targeting succinate metabolism in ischemia/reperfusion injury. Circulation 140:1968–1970. https://doi.org/10.1161/CIRCULATIONAHA.119.042791CrossRefPubMed

33.

Miro-Casas E, Ruiz-Meana M, Agullo E, Stahlhofen S, Rodriguez-Sinovas A, Cabestrero A, Jorge I, Torre I, Vazquez J, Boengler K, Schulz R, Heusch G, Garcia-Dorado D (2009) Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake. Cardiovasc Res 83:747–756. https://doi.org/10.1093/cvr/cvp157CrossRefPubMed

34.

Nicholls DG, Ferguson SJ (2013). In: Bioenergetics, 4 ed. Academic Press, Boston

35.

Prag HA, Aksentijevic D, Dannhorn A, Giles AV, Mulvey JF, Sauchanka O, Du L, Bates G, Reinhold J, Kula-Alwar D, Xu Z, Pellerin L, Goodwin RJA, Murphy MP, Krieg T (2022) Ischemia-selective cardioprotection by malonate for ischemia/reperfusion injury. Circ Res 131:528–541. https://doi.org/10.1161/CIRCRESAHA.121.320717CrossRefPubMedPubMedCentral

36.

Prag HA, Pala L, Kula-Alwar D, Mulvey JF, Luping D, Beach TE, Booty LM, Hall AR, Logan A, Sauchanka V, Caldwell ST, Robb EL, James AM, Xu Z, Saeb-Parsy K, Hartley RC, Murphy MP, Krieg T (2022) Ester prodrugs of malonate with enhanced intracellular delivery protect against cardiac ischemia-reperfusion injury in vivo. Cardiovasc Drugs Ther 36:1–13. https://doi.org/10.1007/s10557-020-07033-6CrossRefPubMed

37.

Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, Konietzka I, Miro E, Totzeck A, Heusch G, Schulz R, Garcia-Dorado D (2006) Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99:93–101. https://doi.org/10.1161/01.RES.0000230315.56904.deCrossRefPubMed

38.

Rodriguez-Sinovas A, Sanchez JA, Gonzalez-Loyola A, Barba I, Morente M, Aguilar R, Agullo E, Miro-Casas E, Esquerda N, Ruiz-Meana M, Garcia-Dorado D (2010) Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism, tolerance to ischemia and preconditioning protection. J Physiol 588:1139–1151. https://doi.org/10.1113/jphysiol.2009.186577CrossRefPubMedPubMedCentral

39.

Rodriguez-Sinovas A, Ruiz-Meana M, Denuc A, Garcia-Dorado D (2018) Mitochondrial Cx43, an important component of cardiac preconditioning. Biochim Biophys Acta 1860:174–181. https://doi.org/10.1016/j.bbamem.2017.06.011CrossRef

40.

Rodríguez-Sinovas A, Sánchez JA, Valls-Lacalle L, Consegal M, Ferreira-González I (2021) Connexins in the heart: regulation, function and involvement in cardiac disease. Int J Mol Sci 22:4413. https://doi.org/10.3390/ijms22094413CrossRefPubMedPubMedCentral

41.

Ruiz-Meana M, Inserte J, Fernandez-Sanz C, Hernando V, Miro-Casas E, Barba I, Garcia-Dorado D (2011) The role of mitochondrial permeability transition in reperfusion-induced cardiomyocyte death depends on the duration of ischemia. Basic Res Cardiol 106:1259–1268. https://doi.org/10.1007/s00395-011-0225-5CrossRefPubMed

42.

Ruiz-Meana M, Rodriguez-Sinovas A, Cabestrero A, Boengler K, Heusch G, Garcia-Dorado D (2008) Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury. Cardiovasc Res 77:325–333. https://doi.org/10.1093/cvr/cvm062CrossRefPubMed

43.

Sanchez JA, Rodriguez-Sinovas A, Barba I, Miro-Casas E, Fernandez-Sanz C, Ruiz-Meana M, Alburquerque-Bejar JJ, Garcia-Dorado D (2013) Activation of RISK and SAFE pathways is not involved in the effects of Cx43 deficiency on tolerance to ischemia-reperfusion injury and preconditioning protection. Basic Res Cardiol 108:351. https://doi.org/10.1007/s00395-013-0351-3CrossRefPubMed

44.

Sanchez JA, Rodriguez-Sinovas A, Fernandez-Sanz C, Ruiz-Meana M, Garcia-Dorado D (2011) Effects of a reduction in the number of gap junction channels or in their conductance on ischemia-reperfusion arrhythmias in isolated mouse hearts. Am J Physiol Heart Circ Physiol 301:H2442–H2453. https://doi.org/10.1152/ajpheart.00540.2011CrossRefPubMed

45.

Schulz R, Boengler K, Totzeck A, Luo Y, Garcia-Dorado D, Heusch G (2007) Connexin 43 in ischemic pre- and postconditioning. Heart Fail Rev 12:261–266. https://doi.org/10.1007/s10741-007-9032-3CrossRefPubMed

46.

Schwanke U, Konietzka I, Duschin A, Li X, Schulz R, Heusch G (2002) No ischemic preconditioning in heterozygous connexin43-deficient mice. Am J Physiol Heart Circ Physiol 283:H1740–H1742. https://doi.org/10.1152/ajpheart.00442.2002CrossRefPubMed

47.

Shimura D, Shaw RM (2022) GJA1-20k and mitochondrial dynamics. Front Physiol 13:867358. https://doi.org/10.3389/fphys.2022.867358CrossRefPubMedPubMedCentral

48.

Stein LR, Imai S (2012) The dynamic regulation of NAD metabolism in mitochondria. Trends Endocrinol Metab 23:420–428. https://doi.org/10.1016/j.tem.2012.06.005CrossRefPubMedPubMedCentral

49.

Tonnesen PT, Hjortbak MV, Lassen TR, Seefeldt JM, Bötker HE, Jespersen NR (2021) Myocardial salvage by succinate dehydrogenase inhibition in ischemia-reperfusion injury depends on diabetes stage in rats. Mol Cell Biochem 476:2675–2684. https://doi.org/10.1007/s11010-021-04108-2CrossRefPubMedPubMedCentral

50.

Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660:171–199. https://doi.org/10.1016/j.bbamem.2003.11.012CrossRefPubMed

51.

Valls-Lacalle L, Barba I, Miro-Casas E, Alburquerque-Bejar JJ, Ruiz-Meana M, Fuertes-Agudo M, Rodriguez-Sinovas A, Garcia-Dorado D (2016) Succinate dehydrogenase inhibition with malonate during reperfusion reduces infarct size by preventing mitochondrial permeability transition. Cardiovasc Res 109:374–384. https://doi.org/10.1093/cvr/cvv279CrossRefPubMed

52.

Valls-Lacalle L, Barba I, Miro-Casas E, Ruiz-Meana M, Rodriguez-Sinovas A, Garcia-Dorado D (2018) Selective inhibition of succinate dehydrogenase in reperfused myocardium with intracoronary malonate reduces infarct size. Sci Rep 8:2442. https://doi.org/10.1038/s41598-018-20866-4CrossRefPubMedPubMedCentral

53.

Valls-Lacalle L, Negre-Pujol C, Rodriguez C, Varona S, Valera-Canellas A, Consegal M, Martinez-Gonzalez J, Rodriguez-Sinovas A (2019) Opposite effects of moderate and extreme Cx43 deficiency in conditional Cx43-deficient mice on angiotensin II-induced cardiac fibrosis. Cells 8:1299. https://doi.org/10.3390/cells8101299CrossRefPubMedPubMedCentral

54.

Wang N, De Vuyst E, Ponsaerts R, Boengler K, Palacios-Prado N, Wauman J, Lai CP, De Bock M, Decrock E, Bol M, Vinken M, Rogiers V, Tavernier J, Evans WH, Naus CC, Bukauskas FF, Sipido KR, Heusch G, Schulz R, Bultynck G, Leybaert L (2013) Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res Cardiol 108:309. https://doi.org/10.1007/s00395-012-0309-xCrossRefPubMed

55.

Wang Y, Oxer D, Hekimi S (2015) Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nat Commun 6:6393. https://doi.org/10.1038/ncomms7393CrossRefPubMed

56.

Wojtovich AP, Brookes PS (2008) The endogenous mitochondrial complex II inhibitor malonate regulates mitochondrial ATP-sensitive potassium channels: implications for ischemic preconditioning. Biochim Biophys Acta 1777:882–889. https://doi.org/10.1016/j.bbabio.2008.03.025CrossRefPubMedPubMedCentral

57.

Yin Z, Burger N, Kula-Alwar D, Aksentijevic D, Bridges HR, Prag HA, Grba DN, Viscomi C, James AM, Mottahedin A, Krieg T, Murphy MP, Hirst J (2021) Structural basis for a complex I mutation that blocks pathological ROS production. Nat Commun 12:707. https://doi.org/10.1038/s41467-021-20942-wCrossRefPubMedPubMedCentral

58.

Zhou Q, Wang Y, Lu Z, He C, Li L, You M, Wang L, Cao T, Zhao Y, Li Q, Mou A, Shu W, He H, Zhao Z, Liu D, Zhu Z, Gao P, Yan Z (2023) Cx43 acts as a mitochondrial calcium regulator that promotes obesity by inducing the polarization of macrophages in adipose tissue. Cell Signal 105:110606. https://doi.org/10.1016/j.cellsig.2023.110606CrossRefPubMed

Titel: Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Cre−ER(T)/fl mice by altering the coenzyme Q pool
verfasst von: Marta Consegal
Elisabet Miró-Casas
Ignasi Barba
Marisol Ruiz-Meana
Javier Inserte
Begoña Benito
Cristina Rodríguez
Freddy G. Ganse
Laura Rubio-Unguetti
Carmen Llorens-Cebrià
Ignacio Ferreira-González
Antonio Rodríguez-Sinovas
Publikationsdatum: 09.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-024-01052-2

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Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43^{Cre−ER(T)/fl} mice by altering the coenzyme Q pool

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