Central role of Mic10 in the mitochondrial contact site and cristae organizing system
05.05.2015
Bohnert M, Zerbes RM, Davies KM, Muehleip AW, Rampelt H, Horvath SE, Boenke T, Kram A, Perschil I, Veenhuis M, Kuehlbrandt W, van der Klei IJ, Pfanner N, van der Laan M.
Cell Metab. 2015;21(5):747-55.
The mitochondrial inner membrane is the main site of ATP production in eukaryotic cells under aerobic conditions. It consists of two distinct domains, the inner boundary membrane and the cristae, which are connected by the conserved mitochondrial contact site and cristae organizing system (MICOS) at the crista junctions. Several lines of evidence suggest that the integral inner membrane proteins Mic60 and Mic10 are the core components of MICOS, but the structural and functional organization of this huge molecular machinery has been unknown. Here we demonstrate that MICOS is composed of at least two distinct subcomplexes, one centered around Mic10, the other around Mic60. The Mic10 protein is engaged in extensive homotypic interactions leading to the formation of large Mic10 oligomers. C onserved glycine motifs in both transmembrane segments of Mic10 are crucial for the stability of these oligomers, while the positively charged loop connecting the transmembrane segments is essential for targeting of Mic10 to the mitochondrial inner membrane. Our data indicate that Mic10 oligomer formation is of crucial importance for mitochondrial membrane architecture. We propose that Mic10 oligomers represent the structural basis of crista junctions and cooperate with other MICOS components to regulate crista junction stability and shape as well as crosstalk between inner and outer mitochondrial membranes.
