Acetic acid induces Sch9p-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Rego, A (Author) Other; Cooper, KF (Author) Other; Snider, J (Author) Other; Hannun, YA (Author) Other; Vitor Costa (Author) ICBAS; Corte Real, M (Author) Other; Chaves, SR (Author) Other

Journal

Title: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Vol. 1863

Pages: 576-583

ISSN: 1388-1981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00N-Q9K

DOI: 10.1016/j.bbalip.2018.02.008

Abstract (EN): Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1 Delta mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 deletion leads to a higher retention of Isc1p in the endoplasmic reticulum upon acetic acid exposure. We also found that the higher resistance of all mutants correlates with higher levels of endogenous mitochondrial phosphorylated long chain bases (LCBPs), suggesting that changing the sphingolipid balance in favour of LCBPs in mitochondria results in increased survival to acetic acid. In conclusion, our results suggest that Sch9p pathways modulate acetic acid-induced cell death, through the regulation of Isc1p cellular distribution, thus affecting the sphingolipid balance that regulates cell fate.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8