Manara - Qatar Research Repository
Browse
DOCUMENT
10.1038_s41467-023-42093-w.pdf (4.02 MB)
DATASET
supp_41467_2023_42093_MOESM10_ESM.xlsx (10.18 kB)
DATASET
supp_41467_2023_42093_MOESM9_ESM.xlsx (52.26 kB)
DATASET
supp_41467_2023_42093_MOESM8_ESM.xlsx (4.32 MB)
DATASET
supp_41467_2023_42093_MOESM7_ESM.xlsx (48.9 kB)
DATASET
supp_41467_2023_42093_MOESM6_ESM.xlsx (78.53 kB)
DATASET
supp_41467_2023_42093_MOESM5_ESM.xlsx (14.71 kB)
DATASET
supp_41467_2023_42093_MOESM4_ESM.xlsx (40.05 kB)
DOCUMENT
supp_41467_2023_42093_MOESM3_ESM.pdf (83.33 kB)
DOCUMENT
supp_41467_2023_42093_MOESM1_ESM.pdf (1.78 MB)
1/0
10 files

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

journal contribution
submitted on 2024-08-22, 10:29 and posted on 2024-08-22, 10:29 authored by 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, Piergiorgio Percipalle

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.

Other Information

Published in: Nature Communications
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1038/s41467-023-42093-w

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU