Reversibility of F1F0 ATP synthase

a. In normally respiring mitochondria, the pmf is high and ATP synthase operates in the direction of ATP synthesis. The ATP is exchanged for cytoplasmic ADP via the adenine nucleotide translocase (ant).

b. During hypoxia, the pmf falls, and the cell relies mainly on homolactic (or alcoholic) fermentation for ATP production. This ATP enters the matrix in exchange for ADP.

F1F0 ATP synthase operates as a proton-translocating ATPase, pumping protons out of the matrix, temporarily sustaining the pmf to support other processes, such as metabolite transport.