Mechanistic insight into heterogeneity of trans-plasma membrane electron transport in cancer cell types
| Autor: | Robert Markus, Alaa Abuawad, Robert Cavanagh, Dong-Hyun Kim, Harry G. Sherman, Hilary M. Collins, James E. Dixon, Frankie J. Rawson, Snow Stolnik, Carolyn Jovanovic |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell type Ascorbate shuttle Lung Neoplasms Cell Biophysics Anion channels Ascorbic Acid Biochemistry Redox Electron Transport 03 medical and health sciences Electron transfer 0302 clinical medicine Ferri-ireduction Cell Line Tumor medicine Electrochemistry Humans Cancer Lung epithelium Chemistry GLUT transport Trans-plasma membrane electron transport (tPMET) Cell Membrane Cell Biology Ascorbic acid Cytochrome b Group Electron transport chain Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell Energy Metabolism Oxidoreductases Reprogramming Oxidation-Reduction |
| Zdroj: | Biochimica et biophysica acta. Bioenergetics. 1860(8) |
| ISSN: | 1879-2650 0005-2728 |
| Popis: | Trans-plasma membrane electron transfer (tMPET) is a process by which reducing equivalents, either electrons or reductants like ascorbic acid, are exported to the extracellular environment by the cell. TPMET is involved in a number of physiological process and has been hypothesised to play a role in the redox regulation of cancer metabolism. Here, we use a new electrochemical assay to elucidate the 'preference' of cancer cells for different trans tPMET systems. This aids in proving a biochemical framework for the understanding of tPMET role, and for the development of novel tPMET-targeting therapeutics. We have delineated the mechanism of tPMET in 3 lung cancer cell models to show that the external electron transfer is orchestrated by ascorbate mediated shuttling via tPMET. In addition, the cells employ a different, non-shuttling-based mechanism based on direct electron transfer via Dcytb. Results from our investigations indicate that tPMETs are used differently, depending on the cell type. The data generated indicates that tPMETs may play a fundamental role in facilitation of energy reprogramming in malignant cells, whereby tPMETs are utilised to supply the necessary energy requirement when mitochondrial stress occurs. Our findings instruct a deeper understanding of tPMET systems, and show how different cancer cells may preferentially use distinguishable tPMET systems for cellular electron transfer processes. |
| Databáze: | OpenAIRE |
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