UCD School of Biomolecular and Biomedical Science, Belfield, Dublin 4, Ireland.
Adv Exp Med Biol. 2012;942:235-47. doi: 10.1007/978-94-007-2869-1_10.
Mitochondria play a key role in energy metabolism and ATP production in many tissues, including skeletal muscle, cardiac muscle, brain and liver. Inherent disorders of mitochondria such as mDNA deletions cause major disruption of metabolism and can result in severe disease phenotypes. However, the incidence of such mDNA based disorders is extremely rare and cannot account for the dramatic rise in human metabolic diseases, which are characterised by defects in energy metabolism. Mitochondrial dysfunction characterized by reduced ATP generation and reduced mitochondrial number in skeletal muscle or reduced ATP generation and mitochondrial stimulus-secretion coupling in the pancreatic beta cell has been implicated in the pathology of chronic metabolic disease associated with type 2 diabetes mellitus and also with aging. Additionally the generation of ROS from mitochondria and other cellular sources may interfere in insulin signaling in muscle, contributing to insulin resistance. Reduced mitochondrial oxidative capacity coupled with increased ROS generation underlies the accumulation of intramuscular fat, insulin resistance and muscle dysfunction in aging. We will review the molecular basis for optimal mitochondrial function or mechanisms of dysfunction and correlate with pathology of identified diseases and aging.
线粒体在许多组织（包括骨骼肌、心肌、脑和肝）的能量代谢和 ATP 产生中发挥着关键作用。线粒体的固有缺陷，如 mDNA 缺失，会导致代谢的严重紊乱，并可能导致严重的疾病表型。然而，这种基于 mDNA 的疾病的发病率非常低，无法解释人类代谢疾病的急剧增加，这些疾病的特征是能量代谢缺陷。线粒体功能障碍的特征是骨骼肌中 ATP 生成减少和线粒体数量减少，或胰腺β细胞中 ATP 生成减少和线粒体刺激-分泌偶联减少，与 2 型糖尿病和衰老相关的慢性代谢疾病的病理学有关。此外，来自线粒体和其他细胞来源的 ROS 的产生可能会干扰肌肉中的胰岛素信号，导致胰岛素抵抗。在衰老过程中，线粒体氧化能力的降低加上 ROS 生成的增加，导致了肌肉内脂肪的积累、胰岛素抵抗和肌肉功能障碍。我们将回顾最佳线粒体功能的分子基础或功能障碍的机制，并与已确定的疾病和衰老的病理学相关联。
