自噬
细胞生物学
脂锚定蛋白
磷脂酰乙醇胺
磷酸化
丝氨酸
串扰
自噬体
化学
生物
生物化学
磷脂
膜
细胞凋亡
物理
光学
磷脂酰胆碱
作者
Prajna Udupa,Abhishek Kumar,Rahul Parit,Debasish Kumar Ghosh
标识
DOI:10.1016/j.metabol.2022.155338
摘要
Homeostasis of autophagy under normal conditions and nutrient stress is maintained by adaptive activation of regulatory proteins. However, the protein-lipid crosstalk that modulates the switch from suppression to activation of autophagy initiation is largely unknown.Here, we show that human diazepam-binding inhibitor (DBI), also known as acyl-CoA binding protein (ACBP), binds to phosphatidylethanolamine of the phagophore membrane under nutrient-rich growth conditions, leading to inhibition of LC3 lipidation and suppression of autophagy initiation. Specific residues, including the conserved tyrosine residues of DBI, interact with phosphatidylethanolamine to stabilize the later molecule in the acyl-CoA binding cavity of the protein. Under starvation, phosphorylation of serine-21 of DBI mediated by the AMP-activated protein kinase results in a drastic reduction in the affinity of the protein for phosphatidylethanolamine. The release of serine-21 phosphorylated DBI from the phagophore upon nutrient starvation restores the high LC3 lipidation flux and maturation of the phagophore to autophagosome.DBI acts as a strategic barrier against overactivation of phagophore maturation under nutrient-rich conditions, while triggering autophagy under nutrient-deficient conditions.
科研通智能强力驱动
Strongly Powered by AbleSci AI