Nature Communications · 15 authors, 7 centres
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This preclinical study using mouse wild-type and nuclear myosin 1 (NM1) knockout cells, together with in vivo tumorigenesis experiments in nude mice, demonstrates that NM1 depletion suppresses the PI3K/AKT/mTOR signaling pathway and mitochondrial transcription factors, causing a metabolic switch from oxidative phosphorylation to aerobic glycolysis and promoting tumor formation.
This preclinical study investigated how nuclear myosin 1 (NM1) regulates mitochondrial function and cellular metabolism using wild-type and NM1 knockout mouse cells, complemented by xenograft experiments in nude mice. The authors found that NM1 depletion dysregulated mitochondrial dynamics: fusion was increased while quality control and mitophagy were decreased, whereas fission was unaffected. NM1 knockout suppressed the PI3K/AKT/mTOR signaling pathway and reduced expression of mitochondrial transcription factors, leading to a metabolic switch from oxidative phosphorylation to aerobic glycolysis as shown by RT-qPCR, fluorometric metabolite quantification, and global metabolomic analysis. Despite suppressed mTOR signaling, NM1 knockout cells proliferated faster and formed tumors in nude mice, suggesting that metabolic reprogramming alone can drive tumorigenesis. The authors propose that NM1 forms a positive feedback loop with mTOR, transcriptionally regulating mTOR and mitochondrial transcription factors TFAM and PGC1α. Limitations include that this is entirely a mouse-based preclinical study with indirect human relevance, and that alternative signaling pathway activation upon mTOR suppression may complicate translational interpretation.
