Mechanistic insight into heterogeneity of trans-plasma membrane electron transport in cancer cell types

Publication date: Available online 20 June 2019Source: Biochimica et Biophysica Acta (BBA) - BioenergeticsAuthor(s): Harry G. Sherman, Carolyn Jovanovic, Alaa Abuawad, Dong-Hyun Kim, Hilary Collins, James E. Dixon, Robert Cavanagh, Robert Markus, Snow Stolnik, Frankie J. RawsonAbstractTrans-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...
Source: Biochimica et Biophysica Acta (BBA) Bioenergetics - Category: Biochemistry Source Type: research