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MARS2 drives metabolic switch of non-small-cell lung cancer cells via interaction with MCU
- Source :
- Redox Biology, Vol 60, Iss , Pp 102628- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Mitochondrial methionyl-tRNA synthetase (MARS2) canonically mediates the formation of fMet-tRNAifMet for mitochondrial translation initiation. Mitochondrial calcium uniporter (MCU) is a major gate of Ca2+ flux from cytosol into the mitochondrial matrix. We found that MARS2 interacts with MCU and stimulates mitochondrial Ca2+ influx. Methionine binding to MARS2 would act as a molecular switch that regulates MARS2-MCU interaction. Endogenous knockdown of MARS2 attenuates mitochondrial Ca2+ influx and induces p53 upregulation through the Ca2+-dependent CaMKII/CREB signaling. Subsequently, metabolic rewiring from glycolysis into pentose phosphate pathway is triggered and cellular reactive oxygen species level decreases. This metabolic switch induces inhibition of epithelial-mesenchymal transition (EMT) via cellular redox regulation. Expression of MARS2 is regulated by ZEB1 transcription factor in response to Wnt signaling. Our results suggest the mechanisms of mitochondrial Ca2+ uptake and metabolic control of cancer that are exerted by the key factors of the mitochondrial translational machinery and Ca2+ homeostasis.
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 60
- Issue :
- 102628-
- Database :
- Directory of Open Access Journals
- Journal :
- Redox Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5bd482d4bba44bd6bbbecfedc52d4d2f
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.redox.2023.102628