TY - JOUR
T1 - The class IA phosphatidylinositol 3-kinase p110-β subunit is a positive regulator of autophagy
AU - Dou, Zhixun
AU - Chattopadhyay, Mohar
AU - Pan, Ji An
AU - Guerriero, Jennifer L.
AU - Jiang, Ya Ping
AU - Ballou, Lisa M.
AU - Yue, Zhenyu
AU - Lin, Richard Z.
AU - Zong, Wei Xing
PY - 2010/11/15
Y1 - 2010/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78349244834&partnerID=8YFLogxK
U2 - 10.1083/jcb.201006056
DO - 10.1083/jcb.201006056
M3 - Article
C2 - 21059846
AN - SCOPUS:78349244834
SN - 0021-9525
VL - 191
SP - 827
EP - 843
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -