期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1793, 期 11, 页码 1776-1786出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2009.09.002
关键词
Mitochondria; Cytochrome c oxidase assembly; F1F0-ATPase; Cox1p translational regulation; Mitochondrial membrane potential
资金
- NIGMS NIH HHS [F31 GM081975, R01 GM071775, GM071775A, F31 GM081975-02, R01 GM071775-04, 1F31-GM081975] Funding Source: Medline
The mitochondrial F1F0-ATP synthase or ATPase is a key enzyme for aerobic energy production in eukaryotic cells. Mutations in ATPase structural and assembly genes are the primary cause of severe human encephalomyopathies, frequently associated with a pleiotropic decrease in cytochrome c oxidase (COX) activity. We have studied the structural and functional constraints underlying the COX defect using Saccharomyces cerevisiae genetic and pharmacological models of ATPase deficiency. In both yeast Delta atp10 and oligomycin-treated wild type cells. COX assembly is selectively impaired in the absence of functional ATPase. The COX biogenesis defect does not involve a primary alteration in the expression of the COX subunits as previously suggested but in their maturation and/or assembly. Expression of COX subunit 1, however, is translationally regulated as in most bona fide COX assembly mutants. Additionally, the COX defect in oligomycin-inhibited ATPase-deficient yeast cells, but not in atp10 cells could be partially prevented by partially dissipating the mitochondrial membrane potential using the uncoupler CCCP. Similar results were obtained with oligomycin-treated and ATP12-deficient human fibroblasts respectively. Our findings imply that fully assembled ATPase and its proton pumping function are both required for COX biogenesis in yeast and mammalian cells through a mechanism independent of Cox1p synthesis. (C) 2009 Elsevier B.V. All rights reserved.
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