Oxidative folding in the mitochondrial intermembrane space: A regulated process important for cell physiology and disease

Mitochondria are fundamental organelles with a complex internal architecture that fulfill important diverse functions including iron–sulfur cluster assembly and cell respiration. Intense work for more than 30 years has identified the key protein import components and the pathways involved in protein targeting and assembly. More recently, oxidative folding has been discovered as one important mechanism for mitochondrial proteostasis whilst several human disorders have been linked to this pathway. We describe the molecular components of this pathway in view of their putative redox regulation and we summarize available evidence on the connections of these pathways to human disorders.