Related Experiment Video
Updated: May 13, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
RRAG GTPases link nutrient availability to gene expression, autophagy and lysosomal biogenesis
Jose A Martina1, Rosa Puertollano
1Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Abstract:
When the levels of intracellular amino acids are high, RRAG GTPases recruit MTORC1 to lysosomes and promote its activation. We found that RRAGs also recruit specific MTORC1 substrates to the lysosomal surface, thus facilitating MTORC1-mediated phosphorylation and regulation. In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy. Redistribution to lysosomes is critical for MTORC1-dependent inactivation of TFEB under nutrient-rich conditions. Therefore, RRAGs play a critical role coordinating nutrient availability and cellular clearance.
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