The yeast AIF homolog Nde1 integrates metabolic and proteostatic signals on the mitochondrial surface and executes cell death

ABSTRACT: Little is known about the proteolytic turnover of mitochondrial proteins under static growth conditions. Combining dynamic isotope labeling and mass spectrometry in yeast cells, we found an exceptionally high turnover for the NADH dehydrogenase Nde1. This homolog of the mammalian apoptosis inducing factor AIF forms two distinct topomers in mitochondria, one residing in the intermembrane space and one cytosol-exposed form that spans the outer membrane. The latter serves as pro-apoptotic factortrigger of cell death with the potential to kill yeast cells in response pro-apoptotic stimuli. The surface-exposed topomer is strongly enriched in respiratory deficient cells and its turnover is executed cooperatively by the cytosolic proteasome and the mitochondrial protease Yme1. Our data suggest that in addition to their role in electron transfer, mitochondrial NADH dehydrogenases such as Nde1 or AIF integrate signals from energy metabolism and cytosolic proteostasis to eliminate compromised individuals from growing cell populations.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Felix Boos  

LAB HEAD: Johannes M. Herrmann

PROVIDER: PXD012531 | Pride | 2019-11-06

REPOSITORIES: Pride