Abstract

Systematic collections of single-gene deletions have been invaluable in uncovering determinants of lifespan in yeast. Overexpression of a single gene does not have such a clear outcome as cancellation of its function but it can lead to a variety of imbalances, deregulations and compensations, and some of them could be important for longevity. We report an experiment in which a genome-wide collection of strains overexpressing a single gene was assayed for chronological lifespan (CLS). Only one group of proteins, those locating to the inner membrane and matrix of mitochondria, tended to extend CLS when abundantly overproduced. We selected two such strains—one overexpressing Qcr7 of the respiratory complex III, the other overexpressing Mrps28 of the small mitoribosomal subunit—and analyzed their transcriptomes. The uncovered shifts in RNA abundance in the two strains were nearly identical and highly suggestive. They implied a distortion in the co-translational assembly of respiratory complexes followed by retrograde signaling to the nucleus. The consequent reprogramming of the entire cellular metabolism towards the resistance to stress resulted in an enhanced ability to persist in a non-proliferating state. Our results show that surveillance of the inner mitochondrial membrane integrity is of outstanding importance for the cell. They also demonstrate that overexpression of single genes could be used effectively to elucidate the mitochondrion-nucleus crosstalk.

Highlights

  • The budding yeast Saccharomyces cerevisiae has been exceptionally useful in classic genetics, recombinant technology and systems biology

  • Our goal was to compare the chronological lifespan (CLS) of multiple yeast strains kept in parallel in a single culture

  • 639 overlapped which was much more than the number expected (94.52) if amplifications of samples coming from the two environments were independent (Fig. 1A)

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Summary

Introduction

The budding yeast Saccharomyces cerevisiae has been exceptionally useful in classic genetics, recombinant technology and systems biology. The mother cell can produce only a limited number of buds and the final count of them is its replicative lifespan (RLS), a measure that has no good analog in metazoans. Another measure of longevity, chronological lifespan (CLS), is the period between the origin and demise of a particular cell. Chronological lifespan (CLS), is the period between the origin and demise of a particular cell It appears universal but does not mean the same for the yeast and metazoan cells. A model does not need to be perfectly fitting as long as it is superbly tractable

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