The class IA phosphatidylinositol 3-kinase p110-β subunit is a positive regulator of autophagy

Zhixun Dou, Mohar Chattopadhyay, Ji An Pan, Jennifer L. Guerriero, Ya Ping Jiang, Lisa M. Ballou, Zhenyu Yue, Richard Z. Lin, Wei Xing Zong

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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)P3, 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.

Original languageEnglish
Pages (from-to)827-843
Number of pages17
JournalJournal of Cell Biology
Volume191
Issue number4
DOIs
StatePublished - 15 Nov 2010

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