Regulatory Interplay Between FtsH, HflKC and YidC in Bacterial Membrane Protein Biogenesis and Quality Control

The quality control of membrane proteins is essential for maintaining cellular homeostasis, as misfolded or damaged proteins can disrupt essential cellular functions. FtsH, a membrane-bound AAA + metalloprotease, is central to bacterial proteostasis, responsible for degrading misfolded or damaged membrane proteins. YidC, a membrane protein insertase, facilitates the folding, insertion, and assembly of membrane proteins into the lipid bilayer. This study investigates the physical interaction between FtsH, HflKC, and YidC, indicating a potential functional relationship between these proteins in maintaining membrane protein quality control in bacteria. Overexpression of YidC in Escherichia coli led to a disruption in the interaction between FtsH and its regulatory proteins HflK and HflC, possibly due to competition for binding sites. This was supported by the depletion of HflK and HflC in both Western blot and mass spectrometry analyses using detergent-solubilized membrane extracts. Additionally, the co-overexpression of FtsH and YidC induced cellular stress, as evidenced by the increased recruitment of stress-related proteins such as GroEL and DnaK. These findings suggest that FtsH and YidC collaborate in membrane protein biogenesis and participate in stress-responsive regulatory mechanisms that contribute to protein homeostasis.