Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complex

Youfen Li, Jeong Soon Park, Jian Hong Deng, Yidong Bai

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Cytochrome c oxidase or complex IV, catalyzes the final step in mitochondrial electron transfer chain, and is regarded as one of the major regulation sites for oxidative phosphorylation. This enzyme is controlled by both nuclear and mitochondrial genomes. Among its 13 subunits, three are encoded by mitochondrial DNA and ten by nuclear DNA. In this work, an RNA interference approach was taken which led to the generation of mouse A9 cell derivatives with suppressed expression of nuclear-encoded subunit IV (COX IV) of this complex. The amounts of this subunit are decrease by 86% to 94% of normal level. A detail biosynthetic and functional analysis of several cell lines with suppressed COX IV expression revealed a loss of assembly of cytochrome c oxidase complex and, correspondingly, a reduction in cytochrome c oxidase-dependent respiration and total respiration. Furthermore, dysfunctional cytochrome c oxidase in the cells leads to a compromised mitochondrial membrane potential, a decreased ATP level, and failure to grow in galactose medium. Interestingly, suppression of COX IV expression also sensitizes the cells to apoptosis. These observations provide the evidence of the essential role of the COX IV subunit for a functional cytochrome c oxidase complex and also demonstrate a tight control of cytochrome c oxidase over oxidative phosphorylation. Finally, our results further shed some insights into the pathogenic mechanism of the diseases caused by dysfunctional cytochrome c oxidase complex.

Original languageEnglish (US)
Pages (from-to)283-291
Number of pages9
JournalJournal of Bioenergetics and Biomembranes
Volume38
Issue number5-6
DOIs
StatePublished - Dec 2006

Keywords

  • ATP synthesis
  • Apoptosis
  • Complex IV assembly
  • Cytochrome c oxidase complex
  • Mitochondria
  • Mitochondrial membrane potential
  • Mitochondrial respiration
  • RNA interference
  • Subunit IV of complex IV

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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