FTSH3 facilitates complex I degradation through a direct interaction with the complex I subunit PSST
Complex I (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation is composed of nuclear and mitochondrial encoded subunits. Its assembly requires sequential addition of subdomains and modules. As it is prone to oxidative damage, complex I subunits continually undergo proteolysis and turnover. We describe the mechanism by which complex I abundance is regulated in a complex I deficient mutant. Using a forward genetic approach we have identified that the complex I Q-module domain subunit PSST, interacts with FTSH3 (Filamentous Temperature Sensitive H3) to mediate the disassembly of the matrix arm domain module for proteolysis and turnover as a means of protein quality control. We show the direct interaction of FTSH3 with PSST and identify the amino acid residues required for this interaction. It is the ATPase function of FTSH3 that is required for the interaction, as the mutation can be compensated by a proteolytically inactive form of FTSH3. Furthermore, it cannot be compensated by FTSH10 that is also located in mitochondria, as the latter does not interact with PSST. This study reveals the mechanistic process at the resolution of the residues involved of how FTSH3 recognises complex I for degradation.