The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis

Biochim Biophys Acta Mol Cell Res. 2018 Feb;1865(2):323-333. doi: 10.1016/j.bbamcr.2017.11.010. Epub 2017 Nov 16.

Abstract

The three mitochondrial-encoded proteins, COX1, COX2, and COX3, form the core of the cytochrome c oxidase. Upon synthesis, COX2 engages with COX20 in the inner mitochondrial membrane, a scaffold protein that recruits metallochaperones for copper delivery to the CuA-Site of COX2. Here we identified the human protein, TMEM177 as a constituent of the COX20 interaction network. Loss or increase in the amount of TMEM177 affects COX20 abundance leading to reduced or increased COX20 levels respectively. TMEM177 associates with newly synthesized COX2 and SCO2 in a COX20-dependent manner. Our data shows that by unbalancing the amount of TMEM177, newly synthesized COX2 accumulates in a COX20-associated state. We conclude that TMEM177 promotes assembly of COX2 at the level of CuA-site formation.

Keywords: COX assembly; COX2 biogenesis; COX20 chaperone; Mitochondria; Oxidative phosphorylation; Respiratory chain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • HEK293 Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • COX20 protein, human
  • Electron Transport Complex IV