A journey through the gateway of polytopic inner membrane proteins: the carrier translocase machinery

Mitochondria are indispensable eukaryotic organelle required for diverse cellular functions. Mitochondrial health depends on the biogenesis of diverse mitochondrial proteins mediated by specialized protein transport machinery from outer and inner membranes called translocases. The carrier translocase (also known as Translocase of the inner membrane 22 (TIM22 complex)) is a unique evolutionary conserved protein translocation machinery involved in importing and integrating complex multispanning inner membrane proteins required for energy generation and cellular metabolic homeostasis. Recent studies have revealed novel characteristics of this machinery, particularly in the higher eukaryotes. In this review, we have discussed the recent advancements in the structure and function of the TIM22 complex in different eukaryotes, with a particular emphasis on the importance of the TIM22 complex in regulating mitochondrial health and pathophysiology.