Difference between revisions of "Juhaszova 2021 Function (Oxf)"

Revision as of 16:56, 21 February 2023

Juhaszova M, Kobrinsky E, Zorov DB, Nuss HB, Yaniv Y, Fishbein KW, de Cabo R, Montoliu L, Gabelli SB, Aon MA, Cortassa S, Sollott SJ (2021) ATP synthase K<sup>+</sup>- and H<sup>+</sup>-fluxes drive ATP synthesis and enable mitochondrial K<sup>+</sup>-"uniporter" function: I. Characterization of ion fluxes. Function (Oxf) 3(2):zqab065. doi: 10.1093/function/zqab065

» PMID: 35229078 Open Access

Juhaszova M, Kobrinsky E, Zorov DB, Nuss HB, Yaniv Y, Fishbein KW, de Cabo R, Montoliu L, Gabelli SB, Aon Miguel A, Cortassa Sonia, Sollott SJ (2021) Function (Oxf)

Abstract: ATP synthase (F₁F_o) 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 F₁F_o-reconstituted proteoliposomes and isolated mitochondria, we show F₁F_o can utilize both ΔΨ_mt-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 F₁F_o 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 F_o 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 F₁F_o 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 ΔΨ_mt) and H⁺ (harnessing its chemical potential energy, Δμ_H) drive ATP generation during normal physiology.

• Bioblast editor: Gnaiger E

Labels: MiParea: Respiration

Preparation: Isolated mitochondria Enzyme: Complex V;ATP synthase Regulation: ATP production, Coupling efficiency;uncoupling, Ion;substrate transport, mt-Membrane potential Coupling state: LEAK, OXPHOS

HRR: Oxygraph-2k

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 |year=2021
 |journal=Function (Oxf)
-|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.
+|abstract=ATP synthase (F<sub>1</sub>F<sub>o</sub>) 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<sub>1</sub>F<sub>o</sub>-reconstituted proteoliposomes and isolated mitochondria, we show F<sub>1</sub>F<sub>o</sub> can utilize both Δ''Ψ''<sub>mt</sub>-driven H<sup>+</sup>- and K<sup>+</sup>-transport to synthesize ATP under physiological pH = 7.2 and K<sup>+</sup> = 140 mEq/L conditions. Purely K<sup>+</sup>-driven ATP synthesis from single F<sub>1</sub>F<sub>o</sub> molecules measured by bioluminescence photon detection could be directly demonstrated along with simultaneous measurements of unitary K<sup>+</sup> currents by voltage clamp, both blocked by specific F<sub>o</sub> inhibitors. In the presence of K<sup>+</sup>, 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<sup>+</sup>: H<sup>+</sup> stoichiometry. The excellent agreement between the functional data obtained from purified F<sub>1</sub>F<sub>o</sub> single molecule experiments and ATP synthase studied in the intact mitochondrion under unaltered OxPhos coupling by K<sup>+</sup> presence, is entirely consistent with K<sup>+</sup> transport through the ATP synthase driving the observed increase in ATP synthesis. Thus, both K<sup>+</sup> (harnessing Δ''Ψ''<sub>mt</sub>) and H<sup>+</sup> (harnessing its chemical potential energy, Δ''μ''<sub>H</sub>) drive ATP generation during normal physiology.
 |editor=Gnaiger E
 }}