小柯机器人

近日，美国普林斯顿大学Joshua D. Rabinowitz及其小组的最新研究表明，呼吸受损时丝氨酸代谢补充NADH。 这一研究成果于2020年3月17日在线发表于《细胞—代谢》杂志。

Author: Lifeng Yang, Juan Carlos Garcia Canaveras, Zihong Chen, Lin Wang, Lingfan Liang, Cholsoon Jang, Johannes A. Mayr, Zhaoyue Zhang, Jonathan M. Ghergurovich, Le Zhan, Shilpy Joshi, Zhixian Hu, Melanie R. McReynolds, Xiaoyang Su, Eileen White, Raphael J. Morscher, Joshua D. Rabinowitz

Issue&Volume: 2020-03-17

Abstract: NADH provides electrons for aerobic ATP production. In cells deprived of oxygen orwith impaired electron transport chain activity, NADH accumulation can be toxic. Tominimize such toxicity, elevated NADH inhibits the classical NADH-producing pathways:glucose, glutamine, and fat oxidation. Here, through deuterium-tracing studies incultured cells and mice, we show that folate-dependent serine catabolism also producessubstantial NADH. Strikingly, when respiration is impaired, serine catabolism throughmethylene tetrahydrofolate dehydrogenase (MTHFD2) becomes a major NADH source. Incells whose respiration is slowed by hypoxia, metformin, or genetic lesions, mitochondrialserine catabolism inhibition partially normalizes NADH levels and facilitates cellgrowth. In mice with engineered mitochondrial complex I deficiency (NDUSF4/), serine’scontribution to NADH is elevated, and progression of spasticity is modestly slowedby pharmacological blockade of serine degradation. Thus, when respiration is impaired,serine catabolism contributes to toxic NADH accumulation.

DOI: 10.1016/j.cmet.2020.02.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30114-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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