| First Author | Dou Z | Year | 2010 |
| Journal | J Cell Biol | Volume | 191 |
| Issue | 4 | Pages | 827-43 |
| PubMed ID | 21059846 | Mgi Jnum | J:166673 |
| Mgi Id | MGI:4849303 | Doi | 10.1083/jcb.201006056 |
| Citation | Dou Z, et al. (2010) The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy. J Cell Biol 191(4):827-43 |
| abstractText | 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-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 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-beta as a positive regulator of autophagy in multicellular organisms. |
