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bioRxiv · 10.64898/2025.12.08.693086

Nutrient/TOR signaling controls Mitochondrial transcription factor A (TFAM) to regulate organismal growth in Drosophila

Sriskanthadevan-Pirahas, S.·Sharma, A.·Khan, S.·Grewal, S. S.
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Abstract

Animals must adapt their growth to fluctuations in nutrient availability to ensure proper development. While nutrient-sensing tissues coordinate organismal growth through inter-organ 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 and metabolic state. 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 metabolic reprogramming, revealing how environmental nutrient availability coordinates organismal growth through tissue-specific metabolic control.

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Sriskanthadevan-Pirahas, S., Sharma, A., Khan, S., Grewal, S. S.. 2025-12-09. Nutrient/TOR signaling controls Mitochondrial transcription factor A (TFAM) to regulate organismal growth in Drosophila. https://doi.org/10.64898/2025.12.08.693086

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