Protein trafficking in the mitochondrial intermembrane space: mechanisms and links to human disease

Mitochondria fulfill a diverse range of functions in cells including oxygen metabolism, homeostasis of inorganic ions and execution of apoptosis. Biogenesis of mitochondria relies on protein import pathways that are ensured by dedicated multiprotein translocase complexes localized in all sub-compartments of these organelles. The key components and pathways involved in protein targeting and assembly have been characterized in great detail over the last three decades. This includes the oxidative folding machinery in the intermembrane space, which contributes to the redox-dependent control of proteostasis. Here, we focus on several components of this system and discuss recent evidence suggesting links to human proteopathy.