生理病理状态下线粒体合成ATP动态调控机制

线粒体是细胞的代谢中心之一，不仅产生大量的ATP为细胞提供能量，还参与多种生物分子（例如核酸、氨基酸、胆固醇和脂肪酸）合成及代谢废物的处理。ATP是细胞重要的“能源货币”，是能量载体和信号分子，参与调节细胞的各种生命活动。动物与人在激烈运动时，ATP消耗速率增加数十倍，但细胞内的ATP仍维持在“设定点”水平，不出现降低。因此，传统生理学观点认为，动物细胞内ATP水平保持恒定。但新的研究结果表明，生物细胞内ATP水平存在波动。生理条件下，增加能量物资（糖、脂和氨基酸等）和氧供，促进线粒体ATP合成，可使细胞内ATP水平出现一过性升高。新的研究证明，在肥胖情况下，由于能量物质的过多供应，细胞内ATP水平出现持续性升高,构成代谢紊乱的源头信号。线粒体ATP合成受多种因素影响，如氧化应激、钙超载、缺氧、线粒体膜通透性增加和线粒体DNA突变等。这些因素与疾病条件下细胞内ATP水平持续降低相关，常见的疾病包括阿尔茨海默症、帕金森疾病、精神分裂症、肿瘤、心衰、全身炎症反应综合征等。本综述简要概述线粒体调节细胞内ATP水平的研究进展，重点讨论造成ATP波动的因素、机制及病理生理学意义。

Dynamic Regulation Mechanisms of Mitochondrial Synthesis of ATP under Physiological and Pathological Conditions

The mitochondrion is one of the metabolic centers of the cells. It not only produces a large amount of ATP, but also participates in the synthesis of various biological molecules (such as nucleic acids, amino acids, cholesterol and fatty acids) and the processing of metabolic wastes. ATP is an important “energy currency”，which serves as a carrier to provide energy to various cellular activities and acts as a signaling molecule to regulate cellular activities. The intracellular level of ATP is believed to be constant as it does not drop in cells when the ATP consumption rate is elevated in the skeletal muscles during exercise. This traditional view is based on the study of ATP in single cells or mitochondria. However, recent studies in mice and humans have shown that the intracellular ATP levels are subject to fluctuation under physiological and pathological conditions, and ATP is a signaling molecule in the feedback regulation of mitochondrial function. Intracellular ATP may increase transiently upon an elevation in substrate supply to mitochondria. In obesity, the ATP level is elevated above the “set point” constantly due to the over-supply of substrates. Intracellular ATP is also affected by factors including oxidative stress, calcium overload, hypoxia, increased permeability of mitochondrial membrane and mitochondrion DNA (mtDNA) mutations, which may all lead to ATP reduction below the set point in diseases. Many diseases are associated with a reduction in the ATP level including Alzheimer’s disease (AD), Parkinson’s disease (PD), Schizophrenia (SP), tumor, heart failure, systemic inflammatory response syndrome (SIRS), etc. This review briefly summarizes the progress in the regulation of intracellular ATP levels, and the significance of ATP fluctuation in the physiological and pathological conditions.