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Juhaszova 2022 Function (Oxf)

From Bioblast
Publications in the MiPMap
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

ยป PMID: 35187492 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 (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 ฮฒ-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 (โˆผ2 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.

โ€ข Bioblast editor: Gnaiger E


Labels: MiParea: Respiration, mtDNA;mt-genetics 



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