Mitochondrial ATP synthase F0 c-ring (ATP synthase c-ring)

The mitochondrial ATP synthase F0 c-ring is a membrane-embedded oligomeric structure composed of multiple c-subunits that functions as a rotary motor within the F1F0-ATP synthase complex (Complex V) (Pagliarani et al., 2016). It plays a central role in cellular bioenergetics by coupling the flow of protons across the inner mitochondrial membrane to the synthesis of ATP (Nesci et al., 2015). Beyond its role in energy production, the c-ring has been identified as a key structural component of the mitochondrial permeability transition pore (mPTP), a high-conductance channel whose opening triggers cell death under conditions of oxidative stress or calcium overload (Alavian et al., 2014). Consequently, the c-ring is a significant therapeutic target in cancer, where its inhibition can deplete ATP in aggressive tumor cells and cancer stem cells, and in neurodegenerative and cardiovascular diseases, where modulating its pore-forming activity may prevent necrotic cell death (Wu et al., 2021; Goldberg et al., 2018). Drugs such as the antibiotic bedaquiline and the laboratory tool oligomycin interact with the c-ring to inhibit proton translocation, while novel small molecules are being explored to selectively target the c-ring's role in mPTP formation to treat ischemia-reperfusion injury and dementia (Zhang et al., 2024; Pagliarani et al., 2016).

Other names

F0 c-ringATP synthase subunit c ringSubunit 9 ringLipid-binding protein ringc-ring rotorMitochondrial ATP synthase subunit c oligomer

Inhibition of the F0 proton channel to block ATP synthesis and hydrolysis; modulation of the mitochondrial permeability transition pore (mPTP) to regulate cell death (Pagliarani et al., 2016; Alavian et al., 2014).