Schwartz Daniel R, Sack Michael N
Translational Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892-1454, United States.
Curr Opin Pharmacol. 2008 Apr;8(2):160-5. doi: 10.1016/j.coph.2007.12.008. Epub 2008 Feb 19.
The dynamic regulation of the structure, function and turnover of mitochondria is recognized as an immutable control node maintaining cellular integrity and homeostasis. The term 'mitohormesis' has recently been coined to describe the adaptive reprogramming of mitochondrial biology in response to low levels of metabolic substrate deprivation to augment subsequent mitochondrial and cellular tolerance to biological stress. Disruption of these regulatory programs gives rise to cardiovascular and neurodegenerative diseases, and augmentation or fine-tuning of these programs may ameliorate mitochondrial and global cellular stress tolerance. This is in part via the regulation of reactive oxygen species, calcium homeostasis, and in response to caloric restriction, the capacity to augment DNA repair. The objective of this manuscript is to briefly review these regulatory programs and to postulate novel therapeutic approaches with the primary goal of modulating mitochondria to enhance tolerance to cardiac ischemic stress.
线粒体结构、功能和更新的动态调节被认为是维持细胞完整性和稳态的一个不变的控制节点。“线粒体应激反应”这一术语最近被创造出来，用于描述线粒体生物学的适应性重编程，以应对低水平的代谢底物剥夺，从而增强随后线粒体和细胞对生物应激的耐受性。这些调节程序的破坏会导致心血管疾病和神经退行性疾病，而增强或微调这些程序可能会改善线粒体和整体细胞应激耐受性。这部分是通过调节活性氧、钙稳态，以及响应热量限制来增强DNA修复能力实现的。本手稿的目的是简要回顾这些调节程序，并提出新的治疗方法，其主要目标是调节线粒体以增强对心脏缺血应激的耐受性。
