Role of MINOS in mitochondrial membrane architecture: cristae morphology and outer membrane interactions differentially depend on mitofilin domains

J Mol Biol. 2012 Sep 14;422(2):183-91. doi: 10.1016/j.jmb.2012.05.004. Epub 2012 May 7.


The mitochondrial inner membrane contains a large protein complex crucial for membrane architecture, the mitochondrial inner membrane organizing system (MINOS). MINOS is required for keeping cristae membranes attached to the inner boundary membrane via crista junctions and interacts with protein complexes of the mitochondrial outer membrane. To study if outer membrane interactions and maintenance of cristae morphology are directly coupled, we generated mutant forms of mitofilin/Fcj1 (formation of crista junction protein 1), a core component of MINOS. Mitofilin consists of a transmembrane anchor in the inner membrane and intermembrane space domains, including a coiled-coil domain and a conserved C-terminal domain. Deletion of the C-terminal domain disrupted the MINOS complex and led to release of cristae membranes from the inner boundary membrane, whereas the interaction of mitofilin with the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM) were enhanced. Deletion of the coiled-coil domain also disturbed the MINOS complex and cristae morphology; however, the interactions of mitofilin with TOM and SAM were differentially affected. Finally, deletion of both intermembrane space domains disturbed MINOS integrity as well as interactions with TOM and SAM. Thus, the intermembrane space domains of mitofilin play distinct roles in interactions with outer membrane complexes and maintenance of MINOS and cristae morphology, demonstrating that MINOS contacts to TOM and SAM are not sufficient for the maintenance of inner membrane architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins / genetics*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism


  • Fcj1 protein, S cerevisiae
  • MIC10 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins