Proteolytic Control of Mitochondrial Biogenesis and Dynamics

Dysfunction of mitochondria has severe cellular consequences and is linked to aging and neurodegeneration in humans. Several surveillance strategies have evolved that limit mitochondrial damage and ensure cellular integrity: intraorganellar proteases conduct protein quality control and exert regulatory functions; the fusion and fission of mitochondrial membranes allows mitochondrial content mixing within a cell; and the autophagic degradation of severely damaged mitochondria protects against apoptosis. The current knowledge on these surveillance strategies and their relevance to human disease will be discussed. The presentation will focus on AAA proteases, conserved ATP-dependent proteolytic complexes in the inner mitochondrial membrane with versatile activities: 1) they conduct protein quality control surveillance; 2) they regulate the assembly of mitochondrial ribosomes acting as processing peptidases; and 3) independent of their proteolytic functions, they mediate the ATP-dependent membrane dislocation of proteins allowing their