Reprogramming of serine, glycine and one-carbon metabolism in cancer

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 10; p. 165841
• Main Authors: Li, Albert M., Ye, Jiangbin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020
• Subjects: Animals; Cancer; Carbon - metabolism; Cellular Reprogramming - physiology; Glycine; Glycine - metabolism; Humans; Metabolic Networks and Pathways; Metabolism; Methionine - metabolism; Mitochondria; Mitochondria - metabolism; Neoplasms - metabolism; One-carbon; Protein Processing, Post-Translational; Serine; Serine - metabolism; Transcription Factors; ALL; GLDC; One-carbon; OXPHOS; KEAP1; ALDH1L2; SGOC; Mitochondria; ATIC; PHGDH; PSPH; EIF2A; SLC1A4/5; tRNA; MS; SIRT5; Metabolism; R-2HG; 1C; TCA; ROS; me-THF; GART; mTORC1; SAM; EWS/FLI; ATF4; MAT; dTTP; Serine; CO2; IDH1/2/3; CRISPR-CAS9; TYMS; Glycine; HIF1/2; LKB1; THF; NRF2; M + n; formyl-THF; PKM2; m-THF; MTHFD1/2; MTHFR; PKCλ/ι; TIC; DHFR; NAD(P)(H); PSAT1; ETC; MTHFD1/2L; DNA; m6A; SFXN1; ATP; SHMT1/2; Cancer
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165841

Metabolic pathways leading to the synthesis, uptake, and usage of the nonessential amino acid serine are frequently amplified in cancer. Serine encounters diverse fates in cancer cells, including being charged onto tRNAs for protein synthesis, providing head groups for sphingolipid and phospholipid synthesis, and serving as a precursor for cellular glycine and one-carbon units, which are necessary for nucleotide synthesis and methionine cycle reloading. This review will focus on the participation of serine and glycine in the mitochondrial one-carbon (SGOC) pathway during cancer progression, with an emphasis on the genetic and epigenetic determinants that drive SGOC gene expression. We will discuss recently elucidated roles for SGOC metabolism in nucleotide synthesis, redox balance, mitochondrial function, and epigenetic modifications. Finally, therapeutic considerations for targeting SGOC metabolism in the clinic will be discussed. •Elevated mitochondrial serine, glycine, and one-carbon (SGOC) metabolism is a feature of many cancers•In addition to supporting biosyntheiss, mitochondrial SGOC metabolism maintains redox homeostasis and mitochondrial function•There exists considerable controversy in the link between SGOC metabolic control of epigenetics•Targeting mitochondrial SGOC is an attractive direction for cancer therapy