MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

Elife. 2015 Apr 28;4:e07739. doi: 10.7554/eLife.07739.

Abstract

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of both MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.

Keywords: MICOS; S. cerevisiae; cardiolipin; cell biology; cristae; mitochondria; respiratory complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiolipins / chemistry
  • Cardiolipins / metabolism*
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism
  • Electron Transport Complex II / chemistry
  • Electron Transport Complex II / genetics
  • Electron Transport Complex II / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / ultrastructure*
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Protein Binding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombination, Genetic
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / ultrastructure*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cardiolipins
  • MIC10 protein, S cerevisiae
  • Membrane Proteins
  • Mic27 protein, S cerevisiae
  • Mitochondrial Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Electron Transport Complex II
  • Electron Transport Complex I