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The mammalian complex I is the largest mitochondrial respiratory chain enzyme composed of 45 constituent subunits. It is the point of entry in the mitochondrial electron transport chain for NADH reducing equivalents, and it behaves as an adaptable pacemaker of respiratory ATP production(1). Mitochondrial respiratory chain complex I is a site of superoxide production during forward electron transfer from NADH to ubiquinone, but it produces more superoxide during reverse electron transfer (RET)(2). Recently, in the mouse liver and heart(3) and in HEK cell lines(4), metabolic labeling studies showed that soluble matrix arm subunits of complex I had shorter half-lives than membrane arm subunits. This is in agreement with the hypothesis that matrix arm subunits might exist as free monomers(5) or in a less stable, smaller sub-complex I(6). We have identified, in the mitochondrial matrix of bovine heart, a soluble part of complex I (sub-complex I) that presents both forward and RET activities. Preliminary results on the activity of the sub-complex I in primary human fibroblast cell cultures from subjects of different ages suggest a possible involvement in aging.
1 Papa S, De Rasmo D. Complex I deficiencies in neurological disorders. Trends Mol. Med. 2013, 19:61-9.
2 Pryde KR, 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. 2011, 286:18056-18065.
3 Kim TY, Wang D, Kim AK, Lau E, Lin AJ, Liem DA, et al. Metabolic labeling reveals proteome dynamics of mouse mitochondria. Mol. Cell. Proteomics 2012, 11:1586-94.
4 Dieteren CE, Koopman WJ, Swarts HG, Peters JG, Maczuga P, Gemst JJ, et al. Subunit-specific incorporation efficiency and kinetics in mitochondrial complex I homeostasis. J. Biol. Chem. 2012, 287:41851-41860.
5 De Rasmo D, Signorile A, Santeramo A, Larizza M, Lattanzio P, Capitanio G, Papa, S. Intramitochondrial adenylyl cyclase controls the turnover of nuclear-encoded subunits and activity of mammalian complex I of the respiratory chain. Biochim. Biophys. Acta 2015, 1853:183-191.
6 Miwa S, Jow H, Baty K, Johnson A, Czapiewski R, Saretzki G. et al. Low abundance of the matrix arm of complex I inmitochondria predicts longevity in mice. Nat. Commun. 2014, 5:3837.
