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Comment
. 2022 Mar 9;3(2):zqac012.
doi: 10.1093/function/zqac012. eCollection 2022.

Rethinking Mitchell's Chemiosmotic Theory: Potassium Dominates Over Proton Flux to Drive Mitochondrial F1Fo-ATP Synthase

Edoardo Bertero  1 , Christoph Maack  1
Affiliations
Comment

Rethinking Mitchell's Chemiosmotic Theory: Potassium Dominates Over Proton Flux to Drive Mitochondrial F1Fo-ATP Synthase

Edoardo Bertero et al. Function (Oxf). .
No abstract available

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Figures

Figure 1.
Figure 1.
The Janus-faced mitochondrial F1Fo-ATP synthase as the master regulator of life and death. The electron transport chain (ETC) receives electrons from NADH and FADH2 to translocate protons (H+) across the inner mitochondrial membran (IMM) to provide the driving force for the F1Fo-ATP synthase to produce ATP. The current studies, suggest that in addition to the H+ motive force (∆μH), the even greater K+-motive force (∆μK) is harnessed to drive ATP production at the ATPase. Through its impact on mitochondrial volume, this optimizes ATP production during increased ATP demand. Pathological concentrations of Ca2+ and/or reactive oxygen species (ROS) trigger cyclophilin D (CyPD) binding to the ATPase and thereby the formation of a permeability transition pore (PTP), which can induce cell death. K+ flux via the ATPase is under the control of survival-related protein Inhibitory Factor 1 (IF1), which in turn is regulated by the Bcl-family proteins Bcl-xL and Mcl-1, to constitute a mitochondrial ATP-dependent K+ current (KATP) that protects against PTP opening during ischemia/reperfusion and other stress conditions. Organ protection during ischemia/reperfusion provided by the canonical mKATP activator diazoxide requires IF1. K+ influx via the ATPase is counterbalanced by K+ extrusion via the K+/H+-exchanger (KHE). In addition to the ATPase, also CCDC51 complexing with ABCB8 constitutes functional mKATP, but without coupling to ATP production.
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