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

Autophagy is an evolutionarily conserved cell re newel process that depends on phosphatidyl inositol 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 beta catalytic subunit is a positive regulator of autophagy Genetic deletion of p110 beta results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart p110 beta does not pro mote 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 beta as a positive regulator of autophagy in multicellular organisms