The MINOS complex: Keeper of mitochondrial membrane architecture

Abstract

Mitochondria are surrounded by two distinct membranes. While the outer membrane confines the organelle, the inner membrane has a key role in cellular energy metabolism. The inner mitochondrial membrane is subdivided into the inner boundary membrane, which is closely opposed to the outer membrane, and large irregular invagi- nations termed cristae. Narrow tubular openings – the crista junctions – connect cristae membrane and inner boundary membrane domains. Additionally, sites of contact between inner boundary and outer mitochondrial membranes are frequently observed. We have recently discovered a mitochondrial inner membrane organizing system (MINOS complex) that is crucial for both, the formation of crista junctions and membrane contact sites. MINOS is composed of six inner membrane proteins: the two highly conserved core subunits Fcj1/mitofilin and Mio10/MINOS1 together with Aim5, Aim13, Aim37 and Mio27. Deletion of FCJ1 or MIO10 in yeast abolishes MINOS formation and leads to a grossly altered mitochondrial ultrastructure with extended stacks of sheet-like cristae membranes and the loss of crista junctions. Moreover, MINOS interacts with several protein complexes of the outer mitochondrial membrane, like the SAM/TOB complex or the TOM complex at membrane contact sites. Formation of MINOS con- tact sites supports the import of precursor proteins from the cytosol into the intermembrane space and outer membrane. A detailed structure/function analysis of Fcj1/mitofilin revealed that membrane tethering, MINOS integrity and formation of crista junctions depend on different Fcj1/mitofilin protein domains.