The versatile role of YidC in membrane protein biosynthesis and quality control

Official URL: https://dx.doi.org/10.1016/j.bbamcr.2025.119956

Membrane proteins are essential for bacterial survival, facilitating vital processes such as energy production, nutrient transport, and cell wall synthesis. YidC is a key player in membrane protein biogenesis, acting as both an insertase and a chaperone to ensure proper protein folding and integration into the lipid bilayer. Its conserved structure and adaptability enable it to mediate co-translational and post-translational protein insertion into the membrane through both Sec-dependent and Sec-independent pathways. In addition to facilitating protein insertion, YidC collaborates with FtsH in protein quality control, preventing the accumulation of misfolded proteins that could impair cellular function. This important relationship between YidC and FtsH is poorly understood, and there is a need for further investigation into their collaboration. Understanding how YidC and FtsH coordinate their roles could provide valuable insights into the links between bacterial membrane protein biogenesis and quality control pathways. Moreover, given its central functions, YidC represents a potential target for antimicrobial development. Small molecules disrupting its function in protein folding and insertion, hold promise. However, achieving bacterial specificity without impacting eukaryotic homologs remains a challenge. Here, we review our current understanding of YidC's structure, molecular function in membrane protein biogenesis and quality control, known interactions and its therapeutic potential.