Synthesis of cytochrome c oxidase subunit 1 is translationally downregulated in the absence of functional F1F0-ATP synthase

Ileana C. Soto, Flavia Fontanesi, Melvys Valledor, Darryl Horn, Rajiv Singh, Antoni Barrientos

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 Δatp10 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.

Original languageEnglish (US)
Pages (from-to)1776-1786
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1793
Issue number11
DOIs
StatePublished - Nov 1 2009

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Keywords

  • Cox1p translational regulation
  • Cytochrome c oxidase assembly
  • FF-ATPase
  • Mitochondria
  • Mitochondrial membrane potential

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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