Abstract
Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high-functioning mitochondria. We report here that mitochondria are functionally segregated even within single mother cells in S. cerevisiae. A high-functioning population of mitochondria accumulates at the tip of the mother cell distal to the bud. We find that the mitochondrial F-box protein (Mfb1p) localizes to mitochondria in the mother tip and is required for mitochondrial anchorage at that site, independent of the previously identified anchorage protein Num1p. Deletion of MFB1 results in loss of the mother-tip-localized mitochondrial population, defects in mitochondrial function and premature replicative ageing. Inhibiting mitochondrial inheritance to buds, by deletion of MMR1, in mfb1Δ cells restores mitochondrial distribution, promotes mitochondrial function and extends replicative lifespan. Our results identify a mechanism that retains a reservoir of high-functioning mitochondria in mother cells and thereby preserves maternal reproductive capacity.
Highlights
Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high-functioning mitochondria
We reasoned that mitochondria that are anchored in the mother cell tip may interact with the anterograde motility apparatus
Previous studies indicate that mitochondria are anchored in the yeast bud tip, and that this process is required for mitochondrial inheritance, mitochondrial quality control during inheritance and yeast lifespan control[7,11]
Summary
Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high-functioning mitochondria. In S. cerevisiae, mother cells produce a limited number of daughters over their lifespan and continue to age with each bud produced; daughter cells are born young, largely independent of the age of their mother cells This finding, that yeast undergo mother–daughter age asymmetry, led to the model that ageing determinants are retained in mother cells, while rejuvenating factors are selectively inherited by buds. Acidification of the vacuole maintains mitochondrial membrane potential in buds but not in mother cells Manipulating either of these mitochondrial quality-control pathways to reduce or increase mitochondrial quality in daughter cells results in shorter or longer replicative lifespans (RLSs), respectively[4,5]
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