ftsh

FtsH is an essential, membrane-anchored ATP-dependent metalloprotease found in many bacteria and in the organelles of eukaryotes, including mitochondria and chloroplasts. Each subunit contains a pair of N-terminal transmembrane helices that anchor the hexameric complex to the inner membrane, followed by a cytoplasmic AAA+ ATPase domain and a C-terminal Zn2+-dependent protease domain. The protease domain features the conserved HExxH zinc-binding motif required for catalysis. As a hexamer, FtsH forms a central proteolytic chamber through which substrate proteins are unfolded and translocated in an ATP-driven process.

Function and mechanism: FtsH participates in general protein quality control by recognizing and degrading misfolded or damaged membrane proteins and other regulatory substrates. The energy from ATP hydrolysis powers substrate unfolding and translocation into the proteolytic chamber, where proteolysis occurs. In bacteria, FtsH also regulates levels of certain key proteins, such as the replication initiator DnaA, linking proteolysis to cell cycle control. Activity can be modulated by accessory factors and adaptors, including HflK and HflC in some species, which influence protease activity in response to cellular conditions.

Distribution and significance: Homologs of FtsH are present in mitochondria and chloroplasts, where they contribute to organellar protein quality control and, in chloroplasts, participate in the photosystem II repair cycle by degrading damaged components. In bacteria, FtsH is often essential for viability, making it a focal point of studies on membrane protein homeostasis and potential antimicrobial targets. The broad conservation and critical role in protein quality control underscore FtsH as a central component of cellular proteostasis.