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Published on: May 28, 2021
Nutrient/TOR signaling controls adipose mitochondrial transcription factor A (TFAM) to regulate organismal growth in
Shrivani Sriskanthadevan-Pirahas1, Shahoon Khan1, Abhishek Sharma1
1Department of Biochemistry and Molecular, Arnie Charbonneau Cancer Institute, and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract:
Animals must adapt their growth to fluctuations in nutrient availability to ensure proper development. While nutrient-sensing tissues coordinate organismal growth through interorgan signaling, the metabolic changes within these tissues that mediate whole-body growth control remain poorly understood. Using Drosophila larvae, we show that TOR (target of rapamycin), a conserved nutrient-sensing kinase, controls developmental growth through regulation of the mitochondrial genome transcription factor TFAM, which controls mitochondrial bioenergetic capacity. We find that nutrient/TOR signaling post-transcriptionally suppresses TFAM protein levels. Furthermore, we find that TOR regulation of TFAM in the larval fat body, a key nutrient-sensing tissue, controls developmental growth. These findings establish a molecular mechanism linking nutrient-sensing pathways to mitochondrial metabolism, revealing how environmental nutrient availability coordinates organismal growth through tissue-specific metabolic control.
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