FTSH PROTEASE 3 facilitates Complex I degradation through a direct interaction with the Complex I subunit PSST

Complex I (CI) (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation, is composed of nuclear- and mitochondrial-encoded subunits. CI assembly occurs via the sequential addition of subdomains and modules. As CI is prone to oxidative damage, its subunits continually undergo proteolysis and turnover. We describe the mechanism by which CI abundance is regulated in a CI-deficient Arabidopsis thaliana mutant. Using a forward genetic approach, we determined that the CI Q-module domain subunit PSST interacts with FTSH PROTEASE 3 (FTSH3) to mediate the disassembly of the matrix arm domain for proteolysis and turnover as a means of protein quality control. We demonstrated the direct interaction of FTSH3 with PSST and identified the amino acid residues required for this interaction. The ATPase function of FTSH3, rather than its proteolytic activity, is required for this interaction, as its mutation was compensated for by a proteolytically inactive form of FTSH3. This study reveals the mechanistic process by which FTSH3 recognizes CI for degradation at amino acid resolution. FTSH PROTEASE 3 directly interacts with the Complex I (CI) (NADH dehydrogenase) subunit PSST, to facilitate the disassembly of the CI matrix arm domain for turnover in the face of oxidative damage.

Automated summary

This study describes the mechanism by which the abundance of Complex I (CI) is regulated in a CI-deficient Arabidopsis thaliana mutant. The interaction between the CI subunit PSST and FTSH3 facilitates the disassembly of the CI matrix arm domain for turnover, ensuring protein quality control in the face of oxidative damage. The study reveals the molecular process by which FTSH3 recognizes CI for degradation at the amino acid level.