The mitochondrial contact site complex, a determinant of mitochondrial architecture

EMBO J. 2011 Oct 18;30(21):4356-70. doi: 10.1038/emboj.2011.379.

Abstract

Mitochondria are organelles with a complex architecture. They are bounded by an envelope consisting of the outer membrane and the inner boundary membrane (IBM). Narrow crista junctions (CJs) link the IBM to the cristae. OMs and IBMs are firmly connected by contact sites (CS). The molecular nature of the CS remained unknown. Using quantitative high-resolution mass spectrometry we identified a novel complex, the mitochondrial contact site (MICOS) complex, formed by a set of mitochondrial membrane proteins that is essential for the formation of CS. MICOS is preferentially located at the CJs. Upon loss of one of the MICOS subunits, CJs disappear completely or are impaired, showing that CJs require the presence of CS to form a superstructure that links the IBM to the cristae. Loss of MICOS subunits results in loss of respiratory competence and altered inheritance of mitochondrial DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / physiology
  • DNA, Mitochondrial / metabolism
  • Intracellular Membranes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Electron
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Mitochondrial Proteins / physiology
  • Models, Biological
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Multiprotein Complexes / physiology
  • Organisms, Genetically Modified
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / ultrastructure*

Substances

  • DNA, Mitochondrial
  • Membrane Proteins
  • Mitochondrial Proteins
  • Multiprotein Complexes