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Membrane tethering of cytochrome c accelerates apoptotic cell death in yeast
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- Toth, Alexandra, 1989- (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Aufschnaiter, Andreas (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Fedotovskaya, Olga (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- (creator_code:org_t)
- 2020-09-05
- 2020
- English.
- In: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:9
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Intrinsic apoptosis as a modality of regulated cell death is intimately linked to permeabilization of the outer mitochondrial membrane and subsequent release of the protein cytochrome c into the cytosol, where it can participate in caspase activation via apoptosome formation. Interestingly, cytochrome c release is an ancient feature of regulated cell death even in unicellular eukaryotes that do not contain an apoptosome. Therefore, it was speculated that cytochrome c release might have an additional, more fundamental role for cell death signalling, because its absence from mitochondria disrupts oxidative phosphorylation. Here, we permanently anchored cytochrome c with a transmembrane segment to the inner mitochondrial membrane of the yeast Saccharomyces cerevisiae, thereby inhibiting its release from mitochondria during regulated cell death. This cytochrome c retains respiratory growth and correct assembly of mitochondrial respiratory chain supercomplexes. However, membrane anchoring leads to a sensitisation to acetic acid-induced cell death and increased oxidative stress, a compensatory elevation of cellular oxygen-consumption in aged cells and a decreased chronological lifespan. We therefore conclude that loss of cytochrome c from mitochondria during regulated cell death and the subsequent disruption of oxidative phosphorylation is not required for efficient execution of cell death in yeast, and that mobility of cytochrome c within the mitochondrial intermembrane space confers a fitness advantage that overcomes a potential role in regulated cell death signalling in the absence of an apoptosome.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Biochemistry
- biokemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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