ATP synthase subunit c

ATP synthase subunit c is a highly conserved, hydrophobic membrane protein forming the core of the Fo (mitochondrial) or Vo (vacuolar) rotary motor in ATP synthase complexes. It assembles into an oligomeric c-ring embedded in the inner mitochondrial membrane, facilitating proton translocation that powers ATP synthesis. The c-ring’s rotation, driven by proton gradients, is mechanically coupled to the catalytic F1 domain, enabling energy conversion. In humans, it is encoded by three nuclear genes, all producing an identical mature protein. Besides its physiological role, the c subunit is implicated in pathological mitochondrial membrane permeabilization, cell death, and certain lysosomal storage diseases. Its inhibition in pathogens serves as a target for antibiotics like bedaquiline, but non-selective inhibition poses a therapeutic risk due to potential systemic mitochondrial toxicity.

Other names

proteolipid subunit csubunit 916 kDa proteolipidATP5G1 (human gene)ATP5G2ATP5G3ATPase c subunitc subunit of Fo/Vo complex

Bedaquiline: binds to c-ring, inhibiting proton translocation and ATP synthesis in mycobacteria; DCCD: covalently modifies a key glutamate/aspartate in the c subunit, blocking proton translocation; Inhibitors of mitochondrial permeability transition: target c-ring’s role in pore formation, potentially preventing cell death.