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Newly imported prot...
Newly imported proteins in mitochondria are particularly sensitive to aggregation
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- Vazquez-Calvo, Carmela, 1983- (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Kohler, Verena (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,University of Graz, Austria
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- Höög, Johanna L, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Büttner, Sabrina, 1978- (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Ott, Martin, 1974- (författare)
- Gothenburg University,Göteborgs universitet,Stockholms universitet,Institutionen för biokemi och biofysik,University of Gothenburg, Sweden,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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(creator_code:org_t)
- John Wiley & Sons, 2023
- 2023
- Engelska.
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 238:3
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- Aim: A functional proteome is essential for life and maintained by protein quality control (PQC) systems in the cytosol and organelles. Protein aggregation is an indicator of a decline of PQC linked to aging and disease. Mitochondrial PQC is critical to maintain mitochondrial function and thus cellular fitness. How mitochondria handle aggregated proteins is not well understood. Here we tested how the metabolic status impacts on formation and clearance of aggregates within yeast mitochondria and assessed which proteins are particularly sensitive to denaturation.Methods: Confocal microscopy, electron microscopy, immunoblotting and genetics were applied to assess mitochondrial aggregate handling in response to heat shock and ethanol using the mitochondrial disaggregase Hsp78 as a marker for protein aggregates.Results: We show that aggregates formed upon heat or ethanol stress with different dynamics depending on the metabolic state. While fermenting cells displayed numerous small aggregates that coalesced into one large foci that was resistant to clearance, respiring cells showed less aggregates and cleared these aggregates more efficiently. Acute inhibition of mitochondrial translation had no effect, while preventing protein import into mitochondria by inhibition of cytosolic translation prevented aggregate formation.Conclusion: Collectively, our data show that the metabolic state of the cells impacts the dynamics of aggregate formation and clearance, and that mainly newly imported and not yet assembled proteins are prone to form aggregates. Because mitochondrial functionality is crucial for cellular metabolism, these results highlight the importance of efficient protein biogenesis to maintain the mitochondrial proteome operational during metabolic adaptations and cellular stress.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- aggregates
- aging
- cellular stress
- Hsp78
- metabolism
- mitochondria
- protein quality control
- proteostasis
- aggregates
- aging
- cellular stress
- Hsp78
- metabolism
- mitochondria
- protein quality control
- proteostasis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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