ATP Synthase K+- and H+-Fluxes Drive ATP Synthesis and Enable Mitochondrial K+-“Uniporter” Function: I. Characterization of Ion Fluxes

Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B Zorov, H Bradley Nuss, Yael Yaniv, Kenneth W Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B Gabelli, Miguel A Aon, Sonia Cortassa, Steven J Sollott

Function2/24/2022·DOI·Read paper

Abstract

Abstract ATP synthase (F1Fo) synthesizes daily our body's weight in ATP, whose production-rate can be transiently increased several-fold to meet changes in energy utilization. Using purified mammalian F1Fo-reconstituted proteoliposomes and isolated mitochondria, we show F1Fo can utilize both ΔΨm-driven H+- and K+-transport to synthesize ATP under physiological pH = 7.2 and K+ = 140 mEq/L conditions. Purely K+-driven ATP synthesis from single F1Fo molecules measured by bioluminescence photon detection could be directly demonstrated along with simultaneous measurements of unitary K+ currents by voltage clamp, both blocked by specific Fo inhibitors. In the presence of K+, compared to osmotically-matched conditions in which this cation is absent, isolated mitochondria display 3.5-fold higher rates of ATP synthesis, at the expense of 2.6-fold higher rates of oxygen consumption, these fluxes being driven by a 2.7:1 K+: H+ stoichiometry. The excellent agreement between the functional data obtained from purified F1Fo single molecule experiments and ATP synthase studied in the intact mitochondrion under unaltered OxPhos coupling by K+ presence, is entirely consistent with K+ transport through the ATP synthase driving the observed increase in ATP synthesis. Thus, both K+ (harnessing ΔΨm) and H+ (harnessing its chemical potential energy, ΔμH) drive ATP generation during normal physiology.

Make this part of your paper trail

Save this paper to a shelf, write a review, and keep your own notes.

Community Ratings

★5(1 rating)

★★★★★

1 rating

Community Reviews

No reviews yet. Be the first to review this paper!