Juhaszova 2022 Function (Oxf): Difference between revisions
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{{Publication | {{Publication | ||
|title=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 (2022) ATP synthase K+- and H+-fluxes drive ATP synthesis and enable mitochondrial K+-"uniporter" function: II. Ion and ATP synthase flux regulation. Function (Oxf) 3(2):zqac001. doi: 10.1093/function/zqac001. PMID: 35187492. | |title=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 (2022) ATP synthase K<sup>+</sup>- and H<sup>+</sup>-fluxes drive ATP synthesis and enable mitochondrial K<sup>+</sup>-"uniporter" function: II. Ion and ATP synthase flux regulation. Function (Oxf) 3(2):zqac001. doi: 10.1093/function/zqac001. PMID: 35187492. | ||
|authors=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 | |authors=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 | ||
|year=2022 | |year=2022 | ||
|journal=Function (Oxf) | |journal=Function (Oxf) | ||
|abstract=We demonstrated that ATP synthase serves the functions of a primary mitochondrial K+ "uniporter," i.e., the primary way for K+ to enter mitochondria. This K+ entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via | |abstract=We demonstrated that ATP synthase serves the functions of a primary mitochondrial K<sup>+</sup> "uniporter," i.e., the primary way for K<sup>+</sup> to enter mitochondria. This K<sup>+</sup> entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via IF<sub>1</sub>. We identified a conserved BH3-like domain of IF1 which overlaps its "minimal inhibitory domain" that binds to the β-subunit of F<sub>1</sub>. Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF<sub>1</sub> and exert effects, requiring this interaction, comparable to diazoxide to augment ATP synthase's H<sup>+</sup> and K<sup>+</sup> flux and ATP synthesis. Bcl-xL and Mcl-1, but not Bcl-2, serve as endogenous regulatory ligands of ATP synthase via interaction with IF1 at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial K<sub>ATP</sub>-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF<sub>1</sub>-progenitors, we found that IF<sub>1</sub> is likely an ancient (∼2 Gya) Bcl-family member that evolved from primordial bacteria resident in eukaryotes, corresponding to their putative emergence as symbiotic mitochondria, and functioning to prevent their parasitic ATP consumption inside the host cell. | ||
|editor=Gnaiger E | |editor=Gnaiger E | ||
}} | }} |
Revision as of 16:34, 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 (2022) ATP synthase K+- and H+-fluxes drive ATP synthesis and enable mitochondrial K+-"uniporter" function: II. Ion and ATP synthase flux regulation. Function (Oxf) 3(2):zqac001. doi: 10.1093/function/zqac001. PMID: 35187492. |
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 (2022) Function (Oxf)
Abstract: We demonstrated that ATP synthase serves the functions of a primary mitochondrial K+ "uniporter," i.e., the primary way for K+ to enter mitochondria. This K+ entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via IF1. We identified a conserved BH3-like domain of IF1 which overlaps its "minimal inhibitory domain" that binds to the β-subunit of F1. Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF1 and exert effects, requiring this interaction, comparable to diazoxide to augment ATP synthase's H+ and K+ flux and ATP synthesis. Bcl-xL and Mcl-1, but not Bcl-2, serve as endogenous regulatory ligands of ATP synthase via interaction with IF1 at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial KATP-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF1-progenitors, we found that IF1 is likely an ancient (∼2 Gya) Bcl-family member that evolved from primordial bacteria resident in eukaryotes, corresponding to their putative emergence as symbiotic mitochondria, and functioning to prevent their parasitic ATP consumption inside the host cell.
• Bioblast editor: Gnaiger E
Labels: MiParea: Respiration, mtDNA;mt-genetics
Enzyme: Complex V;ATP synthase
Coupling state: LEAK, OXPHOS