The lysosome: a crucial hub for AMPK and mTORC1 signalling

Bernadette Carroll; Elaine A. Dunlop

doi:10.1042/BCJ20160780

Abstract

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.

AMPK
autophagy
lysosomes
mTORC1
signalling

Abbreviations

α-KG,: α-ketoglutarate;
ALG-2,: asparagine-linked glycosylation 2;
AMPK,: AMP-activated protein kinase;
ATG,: autophagy-related;
DEPTOR,: DEP domain containing mTOR-interacting protein;
ERK,: extracellular signal-regulated kinase;
FLCN,: folliculin;
GAP,: GTPase-activating protein;
GATOR,: GTPase-activating protein activity towards Rags;
GDI,: guanine nucleotide dissociation inhibitor;
GEF,: guanine nucleotide exchange factor;
LAMP,: lysosomal-associated membrane protein;
LAMTOR,: late endosomal/lysosomal adaptor, MAPK and mTOR activator;
LAT1,: L-type amino acid transporter 1;
LC3,: microtubule-associated protein 1A/1B-light chain 3;
LKB1,: liver kinase B1;
MEK,: mitogen-activated protein kinase/ERK kinase;
MITF,: microphthalmia-associated transcription factor;
MO25,: mouse protein 25;
mTORC1,: mechanistic (mammalian) target of rapamycin complex 1;
PAT,: proton-assisted amino acid transporter;
PI3K,: phosphoinositide 3-kinase;
Raptor,: regulatory-associated protein of mTOR;
PI(3,5)P2,: phosphatidylinositol 3,5-bisphosphate;
Rheb,: Ras homologue enriched in brain;
SESN,: sestrin;
SLC3A2,: solute carrier family 3, member 2;
SLC7A5,: solute carrier family 7, member 5;
SNAP,: synaptosomal-associated protein;
SNARE,: soluble N-ethylmaleimide-sensitive factor-activating protein receptor;
STRAD,: Ste20-related adaptor;
STX,: syntaxin;
TFEB,: transcription factor EB;
TRPML1,: transient receptor potential cation channel, mucolipid subfamily;
TSC,: tuberous sclerosis complex;
ULK1,: Unc51-like kinase;
UVRAG,: UV irradiation resistance-associated gene;
VAMP,: vesicle-associated membrane protein;
v-ATPase,: vacuolar H⁺-ATPase.