The Class IA Phosphatidylinositol 3-kinase P110-beta Subunit is a Positive Regulator of Autophagy

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2010 Nov 10

PMID 21059846

Citations 54

Authors

Zhixun Dou

Mohar Chattopadhyay

Ji-An Pan

Jennifer L Guerriero

Ya-Ping Jiang

Lisa M Ballou

Zhenyu Yue

Richard Z Lin

Wei-Xing Zong

Affiliations

Soon will be listed here.

Abstract

Autophagy is an evolutionarily conserved cell renewal process that depends on phosphatidylinositol 3-phosphate (PtdIns(3)P). In metazoans, autophagy is inhibited by PtdIns(3,4,5)P(3), the product of class IA PI3Ks, which mediates the activation of the Akt-TOR kinase cascade. However, the precise function of class IA PI3Ks in autophagy remains undetermined. Class IA PI3Ks are heterodimeric proteins consisting of an 85-kD regulatory subunit and a 110-kD catalytic subunit. Here we show that the class IA p110-β catalytic subunit is a positive regulator of autophagy. Genetic deletion of p110-β results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart. p110-β does not promote autophagy by affecting the Akt-TOR pathway. Rather, it associates with the autophagy-promoting Vps34-Vps15-Beclin 1-Atg14L complex and facilitates the generation of cellular PtdIns(3)P. Our results unveil a previously unknown function for p110-β as a positive regulator of autophagy in multicellular organisms.

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