Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice

Tomas Venit, Oscar Sapkota, Wael Said Abdrabou, Palanikumar Loganathan, Renu Pasricha, Syed Raza Mahmood, Nadine Hosny El Said, Shimaa Sherif, Sneha Thomas, Salah Abdelrazig, Shady Amin, Davide Bedognetti, Youssef Idaghdour, Mazin Magzoub and Piergiorgio Percipalle ()
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Tomas Venit: New York University Abu Dhabi (NYUAD)
Oscar Sapkota: New York University Abu Dhabi (NYUAD)
Wael Said Abdrabou: New York University Abu Dhabi (NYUAD)
Palanikumar Loganathan: New York University Abu Dhabi (NYUAD)
Renu Pasricha: New York University Abu Dhabi (NYUAD)
Syed Raza Mahmood: New York University Abu Dhabi (NYUAD)
Nadine Hosny El Said: New York University Abu Dhabi (NYUAD)
Shimaa Sherif: Research Branch, Sidra Medicine
Sneha Thomas: New York University Abu Dhabi (NYUAD)
Salah Abdelrazig: New York University Abu Dhabi (NYUAD)
Shady Amin: New York University Abu Dhabi (NYUAD)
Davide Bedognetti: Research Branch, Sidra Medicine
Youssef Idaghdour: New York University Abu Dhabi (NYUAD)
Mazin Magzoub: New York University Abu Dhabi (NYUAD)
Piergiorgio Percipalle: New York University Abu Dhabi (NYUAD)

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: Abstract Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.

Date: 2023
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DOI: 10.1038/s41467-023-42093-w

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