TFEB Links Autophagy to Lysosomal Biogenesis

被引：2807

作者：

Settembre, Carmine ^{[1
,2
,3
]}

Di Malta, Chiara ^{[1
]}

Polito, Vinicia Assunta ^{[1
,2
,3
]}

Garcia-Arencibia, Moises ^{[4
]}

Vetrini, Francesco ^{[2
]}

Erdin, Serkan ^{[2
,3
]}

Erdin, Serpil Uckac ^{[2
,3
]}

Huynh, Tuong ^{[2
,3
]}

Medina, Diego ^{[1
]}

Colella, Pasqualina ^{[1
]}

Sardiello, Marco ^{[2
,3
]}

Rubinsztein, David C. ^{[4
]}

Ballabio, Andrea ^{[1
,2
,3
,5
]}

机构：

[1] TIGEM, I-80131 Naples, Italy

[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[3] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

[4] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[5] Univ Naples Federico 2, Dept Pediat, I-80131 Naples, Italy

来源：

SCIENCE | 2011年 / 332卷 / 6036期

基金：

欧洲研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

IN-VIVO; PHOSPHORYLATION SITES; PROTEIN-DEGRADATION; PREDICTION; PATHWAYS; ULK1;

D O I：

10.1126/science.1204592

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. During starvation, the cell expands both compartments to enhance degradation processes. We found that starvation activates a transcriptional program that controls major steps of the autophagic pathway, including autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. Nuclear localization and activity of TFEB were regulated by serine phosphorylation mediated by the extracellular signal-regulated kinase 2, whose activity was tuned by the levels of extracellular nutrients. Thus, a mitogen-activated protein kinase-dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles.

引用

页码：1429 / 1433

页数：5

共 29 条

[1]

A curated compendium of phosphorylation motifs [J].