Proteasome regulation of petite-negativity in fission yeast

Abstract

AbstractMitochondria carry out essential functions in eukaryotic cells. The mitochondrial genome encodes factors critical to support oxidative phosphorylation and mitochondrial protein import necessary for these functions. However, organisms like budding yeast can readily lose their mitochondrial genome, yielding respiration-deficientpetitemutants. The fission yeastSchizosaccharomyces pombeis petite-negative, but some nuclear mutations enable the loss of its mitochondrial genome. Here, we characterize the classicalpetite-positive mutationptp1-1as a loss of function allele of the proteasome 19S regulatory subunit componentmts4/rpn1, involved in the Ubiquitin-dependent degradation pathway. The mutation results in an altered oxidative stress response, with increased levels of oxidized glutathione, and increased levels of mitochondrial and cytoplasmic chaperones. We propose that Ubiquitin-proteasome regulation of chaperones involved in the Unfolded Protein Response and mitochondrial protein import underlies petite-negativity in fission yeast.