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The Yeast AIF Homolog Nde1 Integrates Signals from Metabolism and Proteostasis on the Mitochondrial Surface and Executes Cell Death

47 Pages Posted: 22 May 2019 Sneak Peek Status: Under Review

See all articles by SreeDivya Saladi

SreeDivya Saladi

University of Kaiserslautern - Cell Biology

Felix Boos

University of Kaiserslautern - Cell Biology

Michael Poglitsch

University of Graz - Institute of Molecular Biosciences

Frederik Sommer

University of Kaiserslautern - Molecular Biotechnology and Systems Biology

Timo Mühlhaus

University of Kaiserslautern - Computational Systems Biology

Michael Schroda

University of Kaiserslautern - Molecular Biotechnology and Systems Biology

Frank Madeo

University of Graz - Institute of Molecular Biosciences

Johannes Herrmann

University of Kaiserslautern - Cell Biology

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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 trigger of cell death with the potential to kill yeast cells in response to pro-apoptotic stimuli. The surface-exposed topomer is degraded by the cytosolic proteasome/Cdc48 system and the mitochondrial protease Yme1 in wild type cells, however, it is strongly enriched in respiratory deficient cells. 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.

Keywords: Apoptosis, Apoptosis-inducing factor, mitochondria, NADH:ubiquitin dehydrogenase, protein import, respiration

Suggested Citation

Saladi, SreeDivya and Boos, Felix and Poglitsch, Michael and Sommer, Frederik and Mühlhaus, Timo and Schroda, Michael and Madeo, Frank and Herrmann, Johannes, The Yeast AIF Homolog Nde1 Integrates Signals from Metabolism and Proteostasis on the Mitochondrial Surface and Executes Cell Death (May 20, 2019). MOLECULAR-CELL-D-19-00882. Available at SSRN: https://ssrn.com/abstract=3391470 or http://dx.doi.org/10.2139/ssrn.3391470
This is a paper under consideration at Cell Press and has not been peer-reviewed.

SreeDivya Saladi

University of Kaiserslautern - Cell Biology ( email )

Kaiserslautern
Germany

Felix Boos

University of Kaiserslautern - Cell Biology

Kaiserslautern
Germany

Michael Poglitsch

University of Graz - Institute of Molecular Biosciences ( email )

Humboldtstraße 50/EG
Graz, 8010
Austria

Frederik Sommer

University of Kaiserslautern - Molecular Biotechnology and Systems Biology ( email )

Kaiserslautern
Germany

Timo Mühlhaus

University of Kaiserslautern - Computational Systems Biology ( email )

Kaiserslautern
Germany

Michael Schroda

University of Kaiserslautern - Molecular Biotechnology and Systems Biology ( email )

Kaiserslautern
Germany

Frank Madeo

University of Graz - Institute of Molecular Biosciences ( email )

Humboldtstraße 50/EG
Graz, 8010
Austria

Johannes Herrmann (Contact Author)

University of Kaiserslautern - Cell Biology ( email )

Kaiserslautern
Germany

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