MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol

Kraemer, L.; Dalheimer, N.; Raeschle, M.; Storchova, Z.; Pielage, J.; Boos, F.; Herrmann, J. M.

doi:10.1101/2022.08.02.502474

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bioRxiv · 10.1101/2022.08.02.502474

MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol

Kraemer, L.·Dalheimer, N.·Raeschle, M.·Storchova, Z.·Pielage, J.·Boos, F.·Herrmann, J. M.

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Abstract

Hundreds of mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational reaction. The early processes associated with mitochondrial protein targeting remain poorly understood. Here we show that in bakers yeast, the cytosol has the capacity to transiently store matrix-destined precursors in dedicated deposits which we named MitoStores. MitoStores are strongly enhanced when protein import into mitochondria is competitively inhibited by a clogging of mitochondrial import sites, but also formed under physiological conditions when cells grow on non-fermentable carbon sources. MitoStores are enriched for a specific subset of nuclear encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. MitoStore formation is controlled by the heat shock proteins Hsp42 and Hsp104, potentially to suppress the toxic potential of accumulating mitochondrial precursor proteins. Thus, the cytosolic protein quality control system plays an active role during early stages in mitochondrial protein targeting by the coordinated and localized sequestration of mitochondrial precursor proteins. SummaryThe yeast cytosol can deposit precursors of mitochondrial proteins in specific granules called MitoStores. MitoStores are controlled by the cytosolic chaperone system, in particular by Hsp42 and Hsp104. MitoStore formation suppresses the toxicity arising from non-imported mitochondrial precursor proteins.

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Kraemer, L., Dalheimer, N., Raeschle, M., Storchova, Z., Pielage, J., Boos, F., Herrmann, J. M.. 2022-08-02. MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol. https://doi.org/10.1101/2022.08.02.502474

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