| First Author | Juhaszova M | Year | 2022 |
| Journal | Function (Oxf) | Volume | 3 |
| Issue | 2 | Pages | zqab065 |
| PubMed ID | 35229078 | Mgi Jnum | J:342911 |
| Mgi Id | MGI:7522580 | Doi | 10.1093/function/zqab065 |
| Citation | Juhaszova M, et al. (2022) ATP Synthase K(+)- and H(+)-Fluxes Drive ATP Synthesis and Enable Mitochondrial K(+)-"Uniporter" Function: I. Characterization of Ion Fluxes. Function (Oxf) 3(2):zqab065 |
| abstractText | ATP synthase (F(1)F(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 F(1)F(o)-reconstituted proteoliposomes and isolated mitochondria, we show F(1)F(o) can utilize both DeltaPsi(m)-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 F(1)F(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 F(1)F(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 DeltaPsi(m)) and H(+) (harnessing its chemical potential energy, Deltamu(H)) drive ATP generation during normal physiology. |
