GALTOR Regulates mTOR and AMPK and Links Metabolic and Quality Control Functions of Autophagy in Endomembrane Damage Vojo Deretic Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
The Ser/Thr protein kinases mTOR and AMPK cooperate as apex regulators of numerous metabolic pathways including autophagy. Autophagy fundamentally differs form other metabolic pathways. Autophagy is not only a catabolic/metabolic process but in addition has quality control functions (quality control autophagy; QCA). QCA plays a role in homeostasis of cellular endomembranes, removes surplus or damaged organelles and toxic macromolecular aggregates, and defends the cytoplasm from invading microbes. The dichotomy in metabolic autophagy vs. QCA is not well understood. Recently we undertook a series of studies to address this issue, coming from the perspective of microbial or sterile endomembrane injury. In contrast to the well-known processes of nutritional signals flowing to and from mTOR and AMPK to orchestrate autophagic and other metabolic responses, it is not known whether and how quality control signals affect mTOR and AMPK. We will present our data showing that mTOR is inhibited whereas AMPK is activated by endomembrane damage, using lysosomal and microbial phagosome damage as model systems. We will report the specific molecular mechanism of how lysosomal damage signals are transduced to mTOR and AMPK through a novel signal transduction system termed GALTOR. GALTOR links quality control functions and metabolic functions of mTOR, AMPK, and autophagy.
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