Transsulfuration activity can support cell growth upon extracellular cysteine limitation Journal Article
| Authors: | Zhu, J.; Berisa, M.; Schwörer, S.; Qin, W.; Cross, J. R.; Thompson, C. B. |
| Article Title: | Transsulfuration activity can support cell growth upon extracellular cysteine limitation |
| Abstract: | Cysteine is required by proliferating cells to maintain protein synthesis as well as cellular redox homeostasis. Zhu et al. show that the transsulfuration cysteine biosynthesis pathway can support cell proliferation when extracellular sources of cysteine become limiting, a condition reported to occur in human tumors as they grow in size. © 2019 Elsevier Inc. Cysteine acts both as a building unit for protein translation and as the limiting substrate for glutathione synthesis to support the cellular antioxidant system. In addition to transporter-mediated uptake, cellular cysteine can also be synthesized from methionine through the transsulfuration pathway. Here, we investigate the regulation of transsulfuration and its role in sustaining cell proliferation upon extracellular cysteine limitation, a condition reported to occur in human tumors as they grow in size. We observed constitutive expression of transsulfuration enzymes in a subset of cancer cell lines, while in other cells, these enzymes are induced following cysteine deprivation. We show that both constitutive and inducible transsulfuration activities contribute to the cellular cysteine pool and redox homeostasis. The rate of transsulfuration is determined by the cellular capacity to conduct methylation reactions that convert S-adenosylmethionine to S-adenosylhomocysteine. Finally, our results demonstrate that transsulfuration-mediated cysteine synthesis is critical in promoting tumor growth in vivo. © 2019 Elsevier Inc. |
| Keywords: | methylation; metabolism; glutathione; cysteine; cancer; transsulfuration; redox homeostasis; xct |
| Journal Title: | Cell Metabolism |
| Volume: | 30 |
| Issue: | 5 |
| ISSN: | 1550-4131 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2019-11-05 |
| Start Page: | 865 |
| End Page: | 876.e5 |
| Language: | English |
| DOI: | 10.1016/j.cmet.2019.09.009 |
| PUBMED: | 31607565 |
| PROVIDER: | scopus |
| PMCID: | PMC6961654 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 December 2019 -- Source: Scopus |
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