The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy.
J Cell Biol
; 191(4): 827-43, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-21059846
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-ß catalytic subunit is a positive regulator of autophagy. Genetic deletion of p110-ß results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart. p110-ß 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-ß as a positive regulator of autophagy in multicellular organisms.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Transdução de Sinais
/
Classe Ia de Fosfatidilinositol 3-Quinase
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article