Friederich Malou, Hansell Peter, Palm Fredrik
Department of Medical Cell Biology, Biomedical Center, Box 571, Uppsala SE-751 23, Sweden.
Curr Diabetes Rev. 2009 May;5(2):120-44. doi: 10.2174/157339909788166800.
The role of altered mitochondria function has recently emerged as an important mechanism for the development of diabetic complications. Altered mitochondria function has also been implicated in the ageing process, defective insulin secretion, hypertension, arteriosclerosis, ischemia-reperfusion injury and apoptosis. Normally, the mitochondria are associated with ATP production using primarily pyruvate as the substrate, but recent reports indicate that tissue specific preferences exist. Also, the mitochondria are a substantial source of superoxide production, preferentially during states of elevated intracellular glucose concentrations. The mitochondria function is regulated by several factors including nitric oxide, oxidative stress, mammalian target of rapamycin, ADP and P(i) availability, which result in a complex regulation of ATP production and oxygen consumption, but also superoxide generation. These factors seem to be tissue specific, which warrants a more diverse mechanistic model applying to that specific tissue or cell type. This review presents the basic functions of the mitochondria and focuses on the complex interplay between oxidative stress, nitric oxide and uncoupling proteins in regulating mitochondria function with special focus on diabetes-induced alterations occurring on the mitochondria level.
线粒体功能改变的作用最近已成为糖尿病并发症发生发展的重要机制。线粒体功能改变还与衰老过程、胰岛素分泌缺陷、高血压、动脉硬化、缺血再灌注损伤及细胞凋亡有关。正常情况下，线粒体主要利用丙酮酸作为底物来产生ATP，但最近的报告表明存在组织特异性偏好。此外，线粒体是超氧化物产生的重要来源，在细胞内葡萄糖浓度升高时尤为明显。线粒体功能受多种因素调节，包括一氧化氮、氧化应激、雷帕霉素靶蛋白、ADP和无机磷酸的可用性，这些因素导致对ATP产生、氧消耗以及超氧化物生成的复杂调节。这些因素似乎具有组织特异性，这就需要一个适用于特定组织或细胞类型的更多样化的机制模型。本综述介绍了线粒体的基本功能，并重点关注氧化应激、一氧化氮和解偶联蛋白在调节线粒体功能方面的复杂相互作用，特别关注线粒体水平上由糖尿病引起的改变。
