The lysosome: a crucial hub for AMPK and mTORC1 signalling

被引:149
作者
Carroll, Bernadette [1 ]
Dunlop, Elaine A. [2 ]
机构
[1] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne, Tyne & Wear, England
[2] Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales
关键词
ACTIVATED PROTEIN-KINASE; TRANSFER-RNA SYNTHETASE; AMINO-ACID SUFFICIENCY; RAG GTPASES; TUMOR-SUPPRESSOR; MAMMALIAN AUTOPHAGY; MECHANISTIC TARGET; TSC1-TSC2; COMPLEX; INHIBITS MTORC1; LEUCINE SENSOR;
D O I
10.1042/BCJ20160780
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Much attention has recently been focussed on the lysosome as a signalling hub. Following the initial discovery that localisation of the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), to the lysosome was essential for mTORC1 activation, the field has rapidly expanded to reveal the role of the lysosome as a platform permitting the co-ordination of several homeostatic signalling pathways. Much is now understood about how the lysosome contributes to amino acid sensing by mTORC1, the involvement of the energy-sensing kinase, AMP-activated protein kinase (AMPK), at the lysosome and how both AMPK and mTORC1 signalling pathways feedback to lysosomal biogenesis and regeneration following autophagy. This review will cover the classical role of the lysosome in autophagy, the dynamic signalling interactions which take place on the lysosomal surface and the multiple levels of cross-talk which exist between lysosomes, AMPK and mTORC1.
引用
收藏
页码:1453 / 1466
页数:14
相关论文
共 112 条
[1]   Getting ready for building: signaling and autophagosome biogenesis [J].
Abada, Adi ;
Elazar, Zvulun .
EMBO REPORTS, 2014, 15 (08) :839-852
[2]   Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor [J].
Avruch, Joseph ;
Long, Xiaomeng ;
Lin, Yenshou ;
Ortiz-Vega, Sara ;
Rapley, Joseph ;
Papageorgiou, Angela ;
Oshiro, Noriko ;
Kikkawa, Ushio .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2009, 37 :223-226
[3]   The serine/threonine kinase ULK1 is a target of multiple phosphorylation events [J].
Bach, Markus ;
Larance, Mark ;
James, David E. ;
Ramm, Georg .
BIOCHEMICAL JOURNAL, 2011, 440 :283-291
[4]   A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1 [J].
Bar-Peled, Liron ;
Chantranupong, Lynne ;
Cherniack, Andrew D. ;
Chen, Walter W. ;
Ottina, Kathleen A. ;
Grabiner, Brian C. ;
Spear, Eric D. ;
Carter, Scott L. ;
Meyerson, Matthew ;
Sabatini, David M. .
SCIENCE, 2013, 340 (6136) :1100-1106
[5]   Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels tomTORC1 [J].
Bar-Peled, Liron ;
Schweitzer, Lawrence D. ;
Zoncu, Roberto ;
Sabatini, David M. .
CELL, 2012, 150 (06) :1196-1208
[6]   p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death [J].
Bjorkoy, G ;
Lamark, T ;
Brech, A ;
Outzen, H ;
Perander, M ;
Overvatn, A ;
Stenmark, H ;
Johansen, T .
JOURNAL OF CELL BIOLOGY, 2005, 171 (04) :603-614
[7]   Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex [J].
Bonfils, Gregory ;
Jaquenoud, Malika ;
Bontron, Severine ;
Ostrowicz, Clemens ;
Ungermann, Christian ;
De Virgilio, Claudio .
MOLECULAR CELL, 2012, 46 (01) :105-110
[8]   Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1 [J].
Bridges, Dave ;
Ma, Jing-Tyan ;
Park, Sujin ;
Inoki, Ken ;
Weisman, Lois S. ;
Saltiel, Alan R. .
MOLECULAR BIOLOGY OF THE CELL, 2012, 23 (15) :2955-2962
[9]   p53 target genes Sestrin1 and Sestrin2 connect genotoxic stress and mTOR signaling [J].
Budanov, Andrei V. ;
Karin, Michael .
CELL, 2008, 134 (03) :451-460
[10]   Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD [J].
Budanov, AV ;
Sablina, AA ;
Feinstein, E ;
Koonin, EV ;
Chumakov, PM .
SCIENCE, 2004, 304 (5670) :596-600