ABSTRACT
Mitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains obscure. Here, we discovered that SAM complex directly interacts with MICOS complex to form a supercomplex, SAMICOS, which bridges mitochondrial outer- and inner-membrane by Sam50-Mic19-Mic60 axis. Mic19, a core component of MICOS, establishes mitochondrial outer- and inner-membrane contact by directly interacting with Sam50 and Mic60, and is required for the assembly of SAMICOS by stabilizing and connecting SAM and MICOS. Interestingly, Mic19 is cleaved by mitochondrial protease OMA1 upon mitochondrial stresses. The cleavage of Mic19 leads to SAMICOS disruption, which causes abnormal mitochondrial morphology, loss of crista junctions, and reduced ATP production even in the presence of SAM and MICOS. Importantly, Sam50 acts as an anchoring point at mitochondrial outer-membrane to guide formation of mitochondrial crista junctions. Therefore, we propose a model that SAM complex integrates with MICOS complex to regulate mitochondrial cristae architecture.
Footnotes
↵# Co-first author