| First Author | Juhaszova M | Year | 2022 |
| Journal | Function (Oxf) | Volume | 3 |
| Issue | 2 | Pages | zqac001 |
| PubMed ID | 35187492 | Mgi Jnum | J:338456 |
| Mgi Id | MGI:7512845 | Doi | 10.1093/function/zqac001 |
| Citation | Juhaszova M, et al. (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 |
| abstractText | 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 IF(1). We identified a conserved BH3-like domain of IF(1) which overlaps its "minimal inhibitory domain" that binds to the beta-subunit of F(1). Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF(1) 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 IF(1) at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial K(ATP)-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF(1)-progenitors, we found that IF(1) is likely an ancient ( approximately 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. |
