Abstract
Aggregation processes can cause severe perturbations of cellular homeostasis and are frequently associated with diseases. We performed a comprehensive analysis of mitochondrial quality and function in the presence of aggregation-prone polypeptides. Despite a significant aggregate formation inside mitochondria, we observed only a minor impairment of mitochondrial function. Detoxification of aggregated reporter polypeptides as well as misfolded endogenous proteins inside mitochondria takes place via their sequestration into a specific organellar deposit site we termed intramitochondrial protein quality control compartment (IMiQ). Only minor amounts of endogenous proteins coaggregated with IMiQ deposits and neither resolubilization nor degradation by the mitochondrial protein quality control system were observed. The single IMiQ aggregate deposit was not transferred to daughter cells during cell division. Detoxification of aggregates via IMiQ formation was highly dependent on a functional mitochondrial fission machinery. We conclude that the formation of an aggregate deposit is an important mechanism to maintain full functionality of mitochondria under proteotoxic stress conditions.
© 2018 Bruderek et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Homeostasis
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Mitochondria / metabolism
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Mitochondria / pathology*
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Mitochondria / physiology*
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Mitochondrial Proteins / physiology*
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Organelles / metabolism
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Peptides
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Protein Aggregates / physiology
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Protein Folding
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Proteostasis Deficiencies / metabolism
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Proteostasis Deficiencies / physiopathology
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / metabolism
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Tetrahydrofolate Dehydrogenase / genetics
Substances
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Mitochondrial Proteins
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Peptides
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Protein Aggregates
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Saccharomyces cerevisiae Proteins
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Tetrahydrofolate Dehydrogenase