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ATP Synthase K+- and H+-Fluxes Drive ATP Synthesis and Enable Mitochondrial K+-"Uniporter" Function: I. Characterization of Ion Fluxes.
- Source :
- Function; 2022, Vol. 3 Issue 2, p1-16, 16p
- Publication Year :
- 2022
-
Abstract
- ATP synthase (F<subscript>1</subscript>F<subscript>o</subscript>) 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 F<subscript>1</subscript>F<subscript>o</subscript>-reconstituted proteoliposomes and isolated mitochondria, we show F<subscript>1</subscript>F<subscript>o</subscript> can utilize both ΔΨ<subscript>m</subscript>-driven H<superscript>+</superscript>- and K<superscript>+</superscript>-transport to synthesize ATP under physiological pH = 7.2 and K<superscript>+</superscript> = 140 mEq/L conditions. Purely K<superscript>+</superscript>-driven ATP synthesis from single F<subscript>1</subscript>F<subscript>o</subscript> molecules measured by bioluminescence photon detection could be directly demonstrated along with simultaneous measurements of unitary K<superscript>+</superscript> currents by voltage clamp, both blocked by specific F<subscript>o</subscript> inhibitors. In the presence of K<superscript>+</superscript>, 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<superscript>+</superscript>: H<superscript>+</superscript> stoichiometry. The excellent agreement between the functional data obtained from purified F<subscript>1</subscript>F<subscript>o</subscript> single molecule experiments and ATP synthase studied in the intact mitochondrion under unaltered OxPhos coupling by K<superscript>+</superscript> presence, is entirely consistent with K<superscript>+</superscript> transport through the ATP synthase driving the observed increase in ATP synthesis. Thus, both K<superscript>+</superscript> (harnessing ΔΨ<subscript>m</subscript>) and H<superscript>+</superscript> (harnessing its chemical potential energy, Δμ<subscript>H</subscript>) drive ATP generation during normal physiology. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 26338823
- Volume :
- 3
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Function
- Publication Type :
- Academic Journal
- Accession number :
- 158424822
- Full Text :
- https://doi.org/10.1093/function/zqab065