Back to Search Start Over

Membrane-tethering of cytochrome c accelerates regulated cell death in yeast

Authors :
Martin Ott
Alexandra Toth
Andreas Aufschnaiter
Olga Fedotovskaya
Hannah Dawitz
Pia Ädelroth
Sabrina Büttner
Source :
Cell Death and Disease, Vol 11, Iss 9, Pp 1-16 (2020), Cell Death & Disease
Publication Year :
2020
Publisher :
Nature Publishing Group, 2020.

Abstract

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.

Details

Language :
English
ISSN :
20414889
Volume :
11
Issue :
9
Database :
OpenAIRE
Journal :
Cell Death and Disease
Accession number :
edsair.doi.dedup.....284a903aff0148e3bf7826166b33d28a
Full Text :
https://doi.org/10.1038/s41419-020-02920-0