期刊
MOLECULAR CELL
卷 56, 期 3, 页码 425-435出版社
CELL PRESS
DOI: 10.1016/j.molcel.2014.09.024
关键词
-
资金
- NIH [P30DK063491, R01CA188652, T32HL105373, R01NS087611]
- DOD [W81XWH-13-1-0105]
- Hellman Faculty Fellowship
- Searle Scholar Award
- Medical Research Service
- Department of Veterans Affairs
- VA San Diego Healthcare System
- Seahorse Bioscience
Pyruvate lies at a central biochemical node connecting carbohydrate, amino acid, and fatty acid metabolism, and the regulation of pyruvate flux into mitochondria represents a critical step in intermediary metabolism impacting numerous diseases. To characterize changes in mitochondrial substrate utilization in the context of compromised mitochondrial pyruvate transport, we applied 13 C metabolic flux analysis (MFA) to cells after transcriptional or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC). Despite profound suppression of both glucose and pyruvate oxidation, cell growth, oxygen consumption, and tricarboxylic acid (TCA) metabolism were surprisingly maintained. Oxidative TCA flux was achieved through enhanced reliance on glutaminolysis through malic enzyme and pyruvate dehydrogenase (PDH) as well as fatty acid and branched-chain amino acid oxidation. Thus, in contrast to inhibition of complex I or PDH, suppression of pyruvate transport induces a form of metabolic flexibility associated with the use of lipids and amino acids as catabolic and anabolic fuels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据