Biochemistry, Department of


Date of this Version



Biochemistry, Just Accepted Manuscript DOI: 10.1021/acs.biochem.7b00663 Publication Date (Web): 14 Aug 2017.


Published by American Chemical Society. Copyright © American Chemical Society. Used by permission.


The inner mitochondrial membrane (IM) is among most protein-rich cellular compartments. The metastable IM sub-proteome where the concentration of proteins is approaching oversaturation creates a challenging protein folding environment with high probability for protein malfunction or aggregation. Failure to maintain protein homeostasis in such a setting can impair functional integrity of the mitochondria and drive clinical manifestations. The IM is equipped with a series of highly conserved, proteolytic complexes dedicated to the maintenance of normal protein homeostasis within this mitochondrial sub-compartment. Particularly important is a group of membrane-anchored metallopeptidases commonly known as m-AAA and i-AAA proteases, and the ATP-independent Oma1 protease. Herein, we will summarize current biochemical knowledge about these proteolytic machines and discuss recent advances toward understanding mechanistic aspects of their functioning.