Heterogeneity of Starved Yeast Cells in IF1 Levels Suggests the Role of This Protein in vivo

Abstract

In mitochondria, a small protein IF1 suppresses the hydrolytic activity of ATP synthase and presumably prevents excessive ATP hydrolysis under conditions of energy deprivation. In yeast Saccharomyces cerevisiae, IF1 homologs are encoded by two paralogous genes: INH1 and STF1. INH1 expression is known to aggravate the deleterious effects of mitochondrial DNA (mtDNA) depletion. Surprisingly, no beneficial effects of INH1 and STF1 were documented for yeast so far, and the functions of INH1 and STF1 in wild type cells are unclear. Here, we put forward a hypothesis that INH1 and STF1 bring advantage during the fast start of proliferation after reentry into exponential growth from post-diauxic or stationary phases. We found that yeast cells increase the concentration of both proteins in the post-diauxic phase. Post-diauxic phase yeast cells formed two subpopulations distinct in Inh1p and Stf1p concentrations. Upon exit from the post-diauxic phase cells with high level of Inh1-GFP started growing earlier than cells devoid of Inh1-GFP. However, double deletion of INH1 and STF1 did not increase the lag period necessary for stationary phase yeast cells to start growing after reinoculation into the fresh medium. These results point to a redundancy of the mechanisms preventing uncontrolled ATP hydrolysis during energy deprivation.

F1·Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis

“…In this regard, both the mutual action of inhibitory proteins and ADP(Mg 2+ ) [ 59 , 91 , 92 ] and their independent action on the F 1 ∙F o regulation are considered [ 50 ], but no consensus has been reached so far. Using compounds with a pronounced activating effect on the latent F 1 ∙F o hydrolytic activity, it was concluded that εCTD- and ADP(Mg 2+ )-induced inhibition are mutually exclusive for the membrane-bound Ec F 1 ·F o [ 50 ].…”

Mitochondrial heteroplasmy as a cause of cell-to-cell phenotypic heterogeneity in clonal populations

“…We have also recently demonstrated that post-diauxic yeast cells form two subpopulations characterised by high and low concentrations of mitochondrial ATP-ase inhibitor proteins (Inh1p and Stf1p). Cells with an elevated inhibitor level recovered more rapidly from the stationary phase than their low-level counterparts, at the same time a high concentration of the inhibitor proteins was deleterious under the conditions of mitochondrial dysfunction ( Galkina et al, 2022 ). These examples show that cell culture phenotypic heterogeneity can be detrimental or adaptive depending on which specific phenotypic properties are considered.…”