Physiological Regulation of Organismal Homeostasis
Patrick Jouandin1, Norbert Perrimon1, 2 1Department of Genetics, Harvard Medical School, Boston, MA, USA; 2Howard Hughes Medical Institute, Boston, MA, USA
Organisms must optimize growth by balancing nutrient consumption and supply, which requires precise assessment of intracellular nutrient content. This process involves the TORC1 (Target of Rapamycin Complex 1) pathway that uses a lysosomal nutrient sensor to integrate the availability of both lysosomal and cytosolic nutrients to control anabolism. Metabolism from other organelles such as the tricarboxylic acid (TCA) cycle in the mitochondria largely provides the cells with nutrients used for anabolism. However, whether TORC1 activity is regulated by the TCA cycle to control growth is unclear. We found that, upon starvation, cysteine degradation in the Drosophila fat body, an organ homologous to the liver and adipose tissue in mammals, replenishes TCA cycle intermediates and controls the downregulation of TORC1. Specifically, we provide evidence that cysteine fuels the TCA cycle in the form of pyruvate, and that the cycle intermediate fumarate is necessary and sufficient to suppress TORC1 activity. Altogether, we propose that TORC1 signaling uses a cysteine degradation pathway to integrate mitochondrial-dependent changes in nutrient availability.
Credits: None available.
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