The Spatio-Temporal Organization of Mitochondrial F1FO-ATP Synthase Is Determined by its Activity and Controlled by IF1

Mitochondrial ATP synthase is the major producer of in respiratory cells and maintains mitochondrial membrane potential ΔΨm glycolytic cells. For these purposes, it works forward (ATP synthesis) or reverse mode hydrolysis). These two modes are not necessarily antagonistic. We provide evidence that both functional types can be found within same mitochondria. combined inhibitor studies with high-resolution microscopy, which reveals mobility localization living under different conditions. distribution its inner membrane, especially cristae, was altered when either ATPase function inhibited. The results were consistent independent whether chemical inhibitors (oligomycin, BMS) used, level inhibitory factor IF1 altered, changes activity induced by metabolic modifications. Inhibition resulted increased confinement synthase. Transient overexpression constitutively active (IF1-H49K), inhibits function, reduced mobility, while knockdown led to In addition, strongly influenced pH values. When substrate for respiration limited, tendency more bound enzyme decreased probably due higher oligomerization. summary, we a change synthesis versus hydrolysis associated synthase, being mobile. This suggests concurrent possible sub-compartments IMM, preventing futile cycles. Furthermore, directs only but also spatio-temporal organization