Serine one-carbon catabolism with formate overflow

Meiser, J. et al. (2016) Serine one-carbon catabolism with formate overflow. Science Advances, 2(10), e1601273. (doi:10.1126/sciadv.1601273) (PMID:27819051) (PMCID:PMC5091358)

Meiser, J. et al. (2016) Serine one-carbon catabolism with formate overflow. Science Advances, 2(10), e1601273. (doi:10.1126/sciadv.1601273) (PMID:27819051) (PMCID:PMC5091358)

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Abstract

Serine catabolism to glycine and a one-carbon unit has been linked to the anabolic requirements of proliferating mammalian cells. However, genome-scale modeling predicts a catabolic role with one-carbon release as formate. We experimentally prove that in cultured cancer cells and nontransformed fibroblasts, most of the serine-derived one-carbon units are released from cells as formate, and that formate release is dependent on mitochondrial reverse 10-CHO-THF synthetase activity. We also show that in cancer cells, formate release is coupled to mitochondrial complex I activity, whereas in nontransformed fibroblasts, it is partially insensitive to inhibition of complex I activity. We demonstrate that in mice, about 50% of plasma formate is derived from serine and that serine starvation or complex I inhibition reduces formate synthesis in vivo. These observations transform our understanding of one-carbon metabolism and have implications for the treatment of diabetes and cancer with complex I inhibitors.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Athineos, Mr Dimitris and Vousden, Karen and Gottlieb, Professor Eyal and Van Den Broek, Mr Niels and Vazquez Vazquez, Alexei and Tumanov, Dr Sergey and Blyth, Dr Karen and Labuschagne, Dr Christiaan Fred and Mackay, Dr Gillian and Maddocks, Dr Oliver and Kamphorst, Dr Jurre
Authors: Meiser, J., Tumanov, S., Maddocks, O., Labuschagne, C. F., Athineos, D., Van Den Broek, N., Mackay, G. M., Gottlieb, E., Blyth, K., Vousden, K., Kamphorst, J. J., and Vazquez, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Science Advances 2(10):e1601273
Publisher Policy:Reproduced under a Creative Commons License

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