Аннотация:Mitochondrial FOF1 ATP synthase couples ATP synthesis or hydrolysis to transmembrane proton transport. The primary function of the enzyme is ATP synthesis driven by protonmotive force (pmf) generated by the respiratory chain. If pmf is low, FOF1 works as a proton-pumping ATPase. In yeast, ATPase activity of FOF1 can be suppressed by inhibitory proteins Inh1p and Stf1p, and MgADP (non-competitive ADP-inhibition). These mechanisms may help the cell to preserve ATP upon mitochondrial membrane de-energization. Nonetheless, no direct evidence was presented to support this hypothesis. We found that a point mutation Q263L in β subunit of Saccharomyces cerevisiae FOF1 attenuates ADP-inhibition without major effect on the rate of ATP production by mitochondria. We used this mutation to test the role of ADP-inhibition in the living yeast cell. The mutant strain grew slower and had a longer lag period preceding exponential growth phase after starvation. However, in yeast lacking mitochondrial DNA (ρ0) the effect was reversed: the βQ263L ρ0 mutant grew faster than the wild-type ρ0 yeast [1]. We also investigated the physiological role of Inh1p and Stf1p, two yeast homologs of mammalian ATP synthase inhibitory factor IF1. We examined the cells in which Inh1p or Stp1p were fused to green fluorescent protein (GFP) and found that cells increase the concentration of both Inh1-GFP and Stf1-GFP in the post-diauxic phase. During this phase, the cells formed two subpopulations distinct in Inh1p-GFP and Stf1p-GFP concentration. Upon exit from the post-diauxic phase the cells with high level of Inh1-GFP started growing earlier than cells devoid of Inh1-GFP. However, the genetic deletion of these two factors did not increase the lag period necessary for stationary phase yeast cells to start growing after reinoculation into the fresh medium [2]. The work is supported by Russian Science Foundation grant 2014-00268. [1] A. Lapashina, N. Kashko, V. Zubareva, K. Galkina, O. Markova, D. Knorre, B. Feniouk, Attenuated ADP-inhibition of FOF1 ATPase mitigates manifestations of mitochondrial dysfunction in yeast, BBA Bioenergetics, 1863 (2022) 148544. [2] K. Galkina, V. Zubareva, N. Kashko, A. Lapashina, O. Markova, B. Feniouk, D. Knorre, Heterogeneity of starved yeast cells in IF1 levels suggests the role of this protein in vivo, Frontiers in Microbiology, 13 (2022) 816622.