title: Acute depression of mitochondrial protein synthesis during anoxia: contributions of oxygen sensing, matrix acidification, and redox state.
abstract: Mitochondrial protein synthesis is acutely depressed during anoxia-induced quiescence in embryos of Artemia franciscana. Oxygen deprivation is accompanied in vivo by a dramatic drop in extramitochondrial pH, and both of these alterations strongly inhibit protein synthesis in isolated mitochondria. Here we show that the oxygen dependence is not explained simply by blockage of the electron transport chain or by the increased redox state. Whereas oxygen deprivation substantially depressed protein synthesis within 5 min and resulted in a 77% reduction after 1 h, aerobic incubations with saturating concentrations of cyanide or antimycin A had little effect during the first 20 min and only a modest effect after 1 h (36 and 20% reductions, respectively). Yet the mitochondrial NAD(P)H pools were fully reduced after 2-3 min with all three treatments. This cyanide- and antimycin-insensitive but hypoxia-sensitive pattern of protein synthesis depression suggests the presence of a molecular oxygen sensor within the mitochondrion. Second, we show for the first time that acidification of extramitochondrial pH exerts inhibition on protein synthesis specifically through changes in matrix pH. Matrix pH was 8.2 during protein synthesis assays performed at the extramitochondrial pH optimum of 7.5. When this proton gradient was abolished with nigericin, the extramitochondrial pH optimum for protein synthesis displayed an alkaline shift of approximately 0.7 pH unit. These data suggest the presence of proton-sensitive translational components within the mitochondrion.
authors.affiliation: Department of Environmental, Population, and Organismic Biology, University of Colorado, Boulder, 80309-0334, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Kwast
authors.forename: S C
authors.initials: SC
authors.lastname: Hand
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001156:Artemia / Q000378:metabolism*; D004579:Electron Transport; D004625:Embryo, Nonmammalian; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011190:Potassium Cyanide / Q000494:pharmacology; D014176:Protein Biosynthesis
chemical_list: D000968:Antimycin A; D011190:Potassium Cyanide; D009550:Nigericin