The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation

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

Authors

Barbosa, AD (Author) Other; Pereira, C (Author) Other; Osorio, H (Author) FMUP; Moradas Ferreira, P (Author) Other; Vitor Costa (Author) ICBAS

Journal

Title: Cell Cycle

Vol. 15

Pages: 1620-1630

ISSN: 1538-4101

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 11 Citations

Other information

Authenticus ID: P-00K-NQY

DOI: 10.1080/15384101.2016.1183846

Abstract (EN): Sit4p is the catalytic subunit of a ceramide-activated PP2A-like phosphatase that regulates cell cycle, mitochondrial function, oxidative stress resistance and chronological lifespan in yeast. In this study, we show that hexokinase 2 (Hxk2p) is hyperphosphorylated in sit4 mutants grown in glucose medium by a Snf1p-independent mechanism and Hxk2p-S15A mutation suppresses phenotypes associated with SIT4 deletion, namely growth arrest at G1 phase, derepression of mitochondrial respiration, H2O2 resistance and lifespan extension. Consistently, the activation of Sit4p in isc1 mutants, which has been associated with premature aging, leads to Hxk2p hypophosphorylation, and the expression of Hxk2p-S15E increases the lifespan of isc1 cells. The overall results suggest that Hxk2p functions downstream of Sit4p in the control of cell cycle, mitochondrial function, oxidative stress resistance and chronological lifespan.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11