Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.
Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.
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DOI：
10.1016/j.cell.2014.11.034
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发表时间：
2014-12-04
期刊：
影响因子：
64.5
通讯作者：
Muoio DM
中科院分区：
文献类型：
--
作者：
Muoio DM
正常能量代谢的特征在于葡萄糖和脂肪氧化的周期性变化，因为负责碳燃烧的线粒体机制根据生理和营养情况在替代燃料之间自由切换。这些燃料选择的转变是由代谢和细胞信号传导事件的复杂网络协调的，这些事件使竞争底物之间的微妙串扰和合作能够维持能量和葡萄糖稳态。相比之下，肥胖相关的心脏代谢疾病越来越多地被认为是代谢紊乱，其中营养过载和底物竞争加剧导致线粒体犹豫不决，燃料转换受损和能量失调。这一观点提供了一个推测性的观点的分子起源和病理生理后果的代谢能力。
Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility.