Lysosomal positioning coordinates cellular nutrient responses

Research output: Contribution to journalArticlepeer-review


  • Viktor I Korolchuk
  • Shinji Saiki
  • Maike Lichtenberg
  • Farah H Siddiqi
  • Esteban A Roberts
  • Sara Imarisio
  • Luca Jahreiss
  • Marie Futter
  • Fiona M Menzies
  • Cahir J O'Kane
  • Vojo Deretic
  • David C Rubinsztein

Colleges, School and Institutes


mTOR (mammalian target of rapamycin) signalling and macroautophagy (henceforth autophagy) regulate numerous pathological and physiological processes, including cellular responses to altered nutrient levels. However, the mechanisms regulating mTOR and autophagy remain incompletely understood. Lysosomes are dynamic intracellular organelles intimately involved both in the activation of mTOR complex 1 (mTORC1) signalling and in degrading autophagic substrates. Here we report that lysosomal positioning coordinates anabolic and catabolic responses with changes in nutrient availability by orchestrating early plasma-membrane signalling events, mTORC1 signalling and autophagy. Activation of mTORC1 by nutrients correlates with its presence on peripheral lysosomes that are physically close to the upstream signalling modules, whereas starvation causes perinuclear clustering of lysosomes, driven by changes in intracellular pH. Lysosomal positioning regulates mTORC1 signalling, which in turn influences autophagosome formation. Lysosome positioning also influences autophagosome-lysosome fusion rates, and thus controls autophagic flux by acting at both the initiation and termination stages of the process. Our findings provide a physiological role for the dynamic state of lysosomal positioning in cells as a coordinator of mTORC1 signalling with autophagic flux.


Original languageEnglish
Pages (from-to)453-60
Number of pages8
JournalNature Cell Biology
Issue number4
Publication statusPublished - Apr 2011


  • Autophagy, Food, HeLa Cells, Humans, Lysosomes, Multiprotein Complexes, Proteins, Signal Transduction, TOR Serine-Threonine Kinases