Mitochondrial contact site and cristae organizing system.

Mitochondria possess two membranes of different architecture. The outer membrane surrounds the organelle, whereas the inner membrane consists of two domains. The inner boundary membrane that is adjacent to the outer membrane harbors many protein translocases. The inner membrane cristae form deep invaginations that carry respiratory chain complexes and the ATP synthase. It has remained enigmatic how crista junctions that connect inner boundary membrane and cristae are formed. The identification of a large protein complex, the mitochondrial contact site and cristae organizing system (MICOS), provided important insights. MICOS is a multi-subunit machinery with two core components, Mic10 and Mic60, organized into subcomplexes. The Mic10-containing subcomplex forms the structural basis of crista junctions, whereas the Mic60-containing subcomplex is crucial for connecting mitochondrial inner and outer membranes at contact sites. Numerous diseases have been directly or indirectly linked to MICOS. MICOS forms a network of interactions with further mitochondrial machineries and can be seen as an organizing center of mitochondrial architecture and biogenesis.