Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q(2). Rescue of respiration by Q(2) is a characteristic of mutants blocked in coenzyme Q(6) synthesis. Unlike Q(6) deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations Of Q(6). The physiological significance of earlier observations that purified Coq10p contains bound Q(6) was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q(2). This suggests that in vivo binding of Q(6) by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains over-producing Coq10p. (C) 2010 Elsevier Inc. All rights reserved.

Fundacao de Amparo a Pesquisa de So Paulo (FAPESP)[2007/01092-5]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fundacao de Amparo a Pesquisa de So Paulo (FAPESP)[2006/03713-4]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[470058/2007-2]

National Institutes of Health (NIH)[HL022174]

U.S. National Institutes of Health (NIH)