The lysosome: a crucial hub for AMPK and mTORC1 signalling

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.