Difference between revisions of "Juhaszova 2019 bioRxiv"
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|abstract=ATP synthase ( | |abstract=ATP synthase (F<sub>1</sub>F<sub>o</sub>) synthesizes daily our bodyโs weight in ATP, whose production-rate can be transiently increased several-fold. Using purified mammalian F<sub>1</sub>F<sub>o</sub>-reconstituted proteoliposomes and isolated mitochondria, we show that F<sub>1</sub>F<sub>o</sub> utilizes both H<sup>+</sup>- and K<sup>+</sup>-transport (because of >10<sup>6</sup>-fold K<sup>+</sup> excess vs H<sup>+</sup>) to drive ATP synthesis with the H<sup>+</sup>:K<sup>+</sup> permeability of ~10<sup>6</sup>:1. F<sub>1</sub>F<sub>o</sub> can be upregulated by endogenous survival-related proteins (Bcl-xL, Mcl-1) and synthetic molecules (diazoxide, pinacidil) to increase its chemo-mechanical efficiency via IF<sub>1</sub>. Increasing K<sup>+</sup>- and H<sup>+</sup>-driven ATP synthesis enables F<sub>1</sub>F<sub>o</sub> to operate as a primary mitochondrial K<sup>+</sup>-uniporter regulating energy supply-demand matching, and as the recruitable mitochondrial K<sub>ATP</sub>-channel that can limit ischemia-reperfusion injury. Isolated mitochondria in the presence of K<sup>+</sup> can sustain ~3.5-fold higher ATP-synthesis-flux (vs K<sup>+</sup> absence) driven by a 2.7:1 K<sup>+</sup>:H<sup>+</sup> stoichiometry with unaltered OxPhos coupling. Excellent agreement between F<sub>1</sub>F<sub>o</sub> single-molecule and intact-mitochondria experiments is consistent with K<sup>+</sup>-transport through ATP synthase driving a major fraction of ATP synthesis. | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
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Latest revision as of 06:38, 14 November 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 (2019) ATP synthase K+- and H+-flux drive ATP synthesis and enable mitochondrial K+-uniporter function. bioRxiv doi: https://doi.org/10.1101/355776 . |
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 (2019) bioRxiv
Abstract: ATP synthase (F1Fo) synthesizes daily our bodyโs weight in ATP, whose production-rate can be transiently increased several-fold. Using purified mammalian F1Fo-reconstituted proteoliposomes and isolated mitochondria, we show that F1Fo utilizes both H+- and K+-transport (because of >106-fold K+ excess vs H+) to drive ATP synthesis with the H+:K+ permeability of ~106:1. F1Fo can be upregulated by endogenous survival-related proteins (Bcl-xL, Mcl-1) and synthetic molecules (diazoxide, pinacidil) to increase its chemo-mechanical efficiency via IF1. Increasing K+- and H+-driven ATP synthesis enables F1Fo to operate as a primary mitochondrial K+-uniporter regulating energy supply-demand matching, and as the recruitable mitochondrial KATP-channel that can limit ischemia-reperfusion injury. Isolated mitochondria in the presence of K+ can sustain ~3.5-fold higher ATP-synthesis-flux (vs K+ absence) driven by a 2.7:1 K+:H+ stoichiometry with unaltered OxPhos coupling. Excellent agreement between F1Fo single-molecule and intact-mitochondria experiments is consistent with K+-transport through ATP synthase driving a major fraction of ATP synthesis.
โข Bioblast editor: Plangger M