Biol Chem. 2025 Aug 11.
Mitochondrial function relies heavily on the proper targeting and insertion of nuclear-encoded proteins into the outer mitochondrial membrane (OMM), a process mediated by specialised biogenesis factors known as insertases. These insertases are essential for the membrane integration of α-helical OMM proteins, which contain one or multiple hydrophobic transmembrane segments. While the general mechanisms of mitochondrial protein import are well established, recent research has shed light on the diversity and evolutionary conservation of OMM insertases across eukaryotic lineages. In Saccharomyces cerevisiae, the mitochondrial import (MIM) complex, composed of Mim1 and Mim2, facilitates the integration of various α-helical OMM proteins, often in cooperation with import receptors such as Tom20 and Tom70. In Trypanosoma brucei, the functional MIM counterpart pATOM36 performs a similar role despite lacking sequence and structural homology, reflecting a case of convergent evolution. In mammals, MTCH2 has emerged as the principal OMM insertase, with MTCH1 playing a secondary, partially redundant role. This review provides a comparative analysis of these insertases, emphasising their conserved functionality, species-specific adaptations, and mechanistic nuances.
Keywords: MIM complex; MTCH2; insertases; mitochondrial outer membrane; pATOM36