Question: Which factors determine CI turnover, and how is this process mechanistically regulated?įindings: Using 2 independent Arabidopsis thaliana EMS mutants generated in a CI-defective background, we show that FTSH3, a mitochondrial matrix-facing inner membrane-bound protease, facilitates the unfolding of CI matrix arm subunits for degradation and turnover. Despite recent advances in the structural determination of plant CI, how CI degradation and turnover is regulated remains enigmatic. High redox activity and constant exposure to reactive oxygen species render CI subunits prone to oxidative damage, thereby resulting in a high turnover rate. Complex I (CI), the first entry point and largest complex of the OXPHOS pathway, begins the OXPHOS process by oxidizing the high-energy intermediate NADH and transferring electrons to the mobile electron carrier ubiquinone. This study reveals the mechanistic process by which FTSH3 recognizes CI for degradation at amino acid resolution.īackground: Oxidative phosphorylation (OXPHOS) is the central process of aerobic respiration in plant mitochondria.
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. We demonstrated the direct interaction of FTSH3 with PSST and identified the amino acid residues required for this interaction. 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 describe the mechanism by which CI abundance is regulated in a CI-deficient Arabidopsis thaliana mutant. As CI is prone to oxidative damage, its subunits continually undergo proteolysis and turnover. CI assembly occurs via the sequential addition of subdomains and modules. Complex I (CI) (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation, is composed of nuclear- and mitochondrial-encoded subunits.
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