AFG3-like protein 2

AFG3-like protein 2 (AFG3L2) is an ATP-dependent metalloprotease subunit that assembles into m-AAA protease complexes embedded into the mitochondrial inner membrane. In humans, m-AAA proteases can form either as homohexamers of AFG3L2 or heterohexamers of AFG3L2 and paraplegin. These proteases project their ATPase and protease modules into the mitochondrial matrix, where they can recognize and process both soluble and membrane-bound substrates. Energy is captured from ATP hydrolysis to unfold and translocate polypeptides into a degradation chamber containing six zinc metalloprotease active sites for cleavage. AFG3L2-containing proteases maintain the mitochondrial proteome, balance the stoichiometry of respiratory complexes, and use site-specific cleavage to regulate key cellular events. Importantly, genetic mutations located throughout AFG3L2 are linked to the development of neurodegenerative diseases with diverse phenotypes.