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Galectins Control mTOR in Response to Endomembrane Damage

2018; Elsevier BV; Volume: 70; Issue: 1 Linguagem: Inglês

10.1016/j.molcel.2018.03.009

1097-4164

Jingyue Jia, Yakubu Princely Abudu, Aurore Claude‐Taupin, Yuexi Gu, Suresh Kumar, Seong Won Choi, Ryan Peters, Michal Mudd, Lee Allers, Michelle Salemi, Brett S. Phinney, Terje Johansen, Vojo Deretić,

Signaling Pathways in Disease

Summary The Ser/Thr protein kinase mTOR controls metabolic pathways, including the catabolic process of autophagy. Autophagy plays additional, catabolism-independent roles in homeostasis of cytoplasmic endomembranes and whole organelles. How signals from endomembrane damage are transmitted to mTOR to orchestrate autophagic responses is not known. Here we show that mTOR is inhibited by lysosomal damage. Lysosomal damage, recognized by galectins, leads to association of galectin-8 (Gal8) with the mTOR apparatus on the lysosome. Gal8 inhibits mTOR activity through its Ragulator-Rag signaling machinery, whereas galectin-9 activates AMPK in response to lysosomal injury. Both systems converge upon downstream effectors including autophagy and defense against Mycobacterium tuberculosis . Thus, a novel galectin-based signal-transduction system, termed here GALTOR, intersects with the known regulators of mTOR on the lysosome and controls them in response to lysosomal damage. Video Abstract