Proteolysis of mitochondrial inner membrane proteins

The inner membrane of mitochondria, the protein-richest cellular membrane, is the major site for cellular energy production. It harbours the respiratory chain and ATP synthase complexes, multisubunit protein complexes whose assembly depends on the coordinated expression of nuclearly and mitochondrially encoded subunits. AAA proteases, highly conserved energy-dependent proteolytic machines in the inner membrane of mitochondria, conduct the quality surveillance of these complexes. They form ring-like assemblies with chaperone-like properties and, in concert with various oligopeptidases, mediate the complete turnover of non-assembled membrane proteins after their vectorial dislocation from the membrane. We analyze mechanisms guiding substrate recognition and membrane protein turnover by AAA proteases using biochemical and genetic approaches both in S. cerevisiae and in mice.

 

Proteolytic pathways in mitochondria of S. cerevisiae

Model of the hexameric ring of AAA-domains of the i-AAA protease Yme1