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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 2708345, 14 pages
https://doi.org/10.1155/2017/2708345
Research Article

Stress-Activated Degradation of Sphingolipids Regulates Mitochondrial Function and Cell Death in Yeast

1Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, 46010 Valencia, Spain
2Department of Biotechnology, Instituto de Biología Molecular y Celular de Plantas, Universitat Politècnica de València-CSIC, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain

Correspondence should be addressed to Markus Proft; se.cisc.vbi@tforpm

Received 14 March 2017; Revised 24 May 2017; Accepted 11 June 2017; Published 6 August 2017

Academic Editor: Cungui Mao

Copyright © 2017 Sara Manzanares-Estreder et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sphingolipids are regulators of mitochondria-mediated cell death in higher eukaryotes. Here, we investigate how changes in sphingolipid metabolism and downstream intermediates of sphingosine impinge on mitochondrial function. We found in yeast that within the sphingolipid degradation pathway, the production via Dpl1p and degradation via Hfd1p of hexadecenal are critical for mitochondrial function and cell death. Genetic interventions, which favor hexadecenal accumulation, diminish oxygen consumption rates and increase reactive oxygen species production and mitochondrial fragmentation and vice versa. The location of the hexadecenal-degrading enzyme Hfd1p in punctuate structures all along the mitochondrial network depends on a functional ERMES (endoplasmic reticulum-mitochondria encounter structure) complex, indicating that modulation of hexadecenal levels at specific ER-mitochondria contact sites might be an important trigger of cell death. This is further supported by the finding that externally added hexadecenal or the absence of Hfd1p enhances cell death caused by ectopic expression of the human Bax protein. Finally, the induction of the sphingolipid degradation pathway upon stress is controlled by the Hog1p MAP kinase. Therefore, the stress-regulated modulation of sphingolipid degradation might be a conserved way to induce cell death in eukaryotic organisms.