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

ABSTRACT: Hundreds of nucleus-encoded mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational manner. However, the early processes associated with mitochondrial protein targeting remain poorly understood. Here we show that in Saccharomyces cerevisiae, the cytosol has the capacity to transiently store mitochondrial matrix-destined precursors in dedicated deposits that we termed MitoStores. Competitive inhibition of mitochondrial protein import via clogging of import sites greatly enhances formation of MitoStores, but they also form during physiological cells growth on non-fermentable carbon sources. MitoStores are enriched for a specific subset of nucleus-encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. Our results suggest that MitoStore formation suppresses the toxic potential of aberrantly accumulating mitochondrial precursor proteins, and is controlled by the heat shock proteins Hsp42 and Hsp104. Thus, the cytosolic protein quality control system plays an active role during early stages of mitochondrial protein targeting through the coordinated and localized sequestration of mitochondrial precursor proteins.

SUBMITTER: Ms. Lena Kraemer

PROVIDER: S-SCDT-10_15252-EMBJ_2022112309 | biostudies-other |

REPOSITORIES: biostudies-other

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

Project description:Hundreds of nucleus-encoded mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational manner. However, the early processes associated with mitochondrial protein targeting remain poorly understood. Here, we show that in Saccharomyces cerevisiae, the cytosol has the capacity to transiently store mitochondrial matrix-destined precursors in dedicated deposits that we termed MitoStores. Competitive inhibition of mitochondrial protein import via clogging of import sites greatly enhances the formation of MitoStores, but they also form during physiological cell growth on nonfermentable carbon sources. MitoStores are enriched for a specific subset of nucleus-encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. Our results suggest that MitoStore formation suppresses the toxic potential of aberrantly accumulating mitochondrial precursor proteins and is controlled by the heat shock proteins Hsp42 and Hsp104. Thus, the cytosolic protein quality control system plays an active role during the early stages of mitochondrial protein targeting through the coordinated and localized sequestration of mitochondrial precursor proteins.

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MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol - Data Set 2: Hsp104 AP-MS

Project description:Hundreds of mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational reaction. The early stages in mitochondrial protein targeting are poorly understood. Here we show that in baker’s yeast, the cytosol has the capacity to transiently store matrix-destined precursors in dedicated deposits which we named MitoStores. MitoStores are strongly induced when the import into mitochondria is competitively inhibited by clogging the mitochondrial import sites, but also found under physiological conditions when cells grow on non-fermentable carbon sources. MitoStores contain a specific subset of nuclear encoded mitochondrial proteins, in particular those with N-terminal mitochondrial targeting sequences. The cytosolic heat shock proteins Hsp42 and Hsp104 control MitoStore formation, thereby suppressing the toxic potential of accumulating mitochondrial precursor proteins. Thus, the cytosolic protein quality system plays an active role during early stages in mitochondrial protein targeting by the coordinated localized sequestration of mitochondrial precursor proteins.

2022-10-15 | PXD035762 | Pride

MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol - Data Set 1: Global Proteome TMT

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The mitochondrial chaperone protein TRAP1 mitigates ?-Synuclein toxicity.

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Human polypyrimidine tract-binding protein interacts with mitochondrial tRNA(Thr) in the cytosol.

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