Ceramide signaling targets the PP2A-like protein phosphatase Sit4p to impair vacuolar function, vesicular trafficking and autophagy in Isc1p deficient cells

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Vítor Teixeira (Author) ICBAS; Tânia Medeiros (Author) Other; Rita Vilaça (Author) ICBAS; João Ferreira (Author) ICBAS; Pedro Gaspar Ferreira (Author) ICBAS; Vitor Costa (Author) ICBAS

Journal

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

Vol. 1861 No. 1

Pages: 21-33

ISSN: 1388-1981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 10 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-00G-SD3

DOI: 10.1016/j.bbalip.2015.10.004

Abstract (EN): The vacuoles play important roles in cellular homeostasis and their functions include the digestion of cytoplasmic material and organelles derived from autophagy. Conserved nutrient signaling pathways regulate vacuolar function and autophagy, ensuring normal cell and organismal development and aging. Recent evidence implicates sphingolipids in the modulation of these processes, but the impact of ceramide signaling on vacuolar dynamics and autophagy remains largely unknown. Here, we show that yeast cells lacking Isc1p, an orthologue of mammalian neutral sphingomyelinase type 2, exhibit vacuolar fragmentation and dysfunctions, namely decreased Pep4p-mediated proteolysis and V-ATPase activity, which impairs vacuolar acidification. Moreover, these phenotypes are suppressed by downregulation of the ceramide-activated protein phosphatase Sit4p. The isc1 Delta cells also exhibit defective Cvt and vesicular trafficking in a Sit4p-dependent manner, ultimately contributing to a reduced autophagic flux. Importantly, these phenotypes are also suppressed by downregulation of the nutrient signaling kinase TORC1, which is known to inhibit Sit4p and autophagy, or Sch9p. These results support a model in which Sit4p functions downstream of Isc1p in a TORC1-independent, ceramide-dependent signaling branch that impairs vacuolar function and vesicular trafficking, leading to autophagic defects in yeast

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13