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The class IA phosphatidylinositol 3-kinase p110-β subunit is a positive regulator of autophagy.
- Source :
-
Journal of Cell Biology . 11/15/2010, Vol. 191 Issue 4, p827-843. 17p. - Publication Year :
- 2010
-
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 85kD regulatory subunit and a 110kD 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 autophagypromoting 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219525
- Volume :
- 191
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 55669707
- Full Text :
- https://doi.org/10.1083/jcb.201006056