McLeod Christopher J, Pagel Ines, Sack Michael N
Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892-1454, USA.
Trends Cardiovasc Med. 2005 Apr;15(3):118-23. doi: 10.1016/j.tcm.2005.05.001.
The resurgence of mitochondrial biology research stems from the realization that the distinct regulation of mitochondria to meet diverse homeostatic demands is driven by exquisite biochemical and molecular control mechanisms. This program termed mitochondrial biogenesis is integral to orchestrating mitochondrial function and appears to exhibit adaptive remodeling following biomechanical and oxidative stress. The major bioenergetic function of mitochondria partitions the final utilization of oxygen between oxidative phosphorylation and reactive oxygen species. As disruption in oxidative phosphorylation and excessive reactive oxygen species contribute to cardiac ischemia-reperfusion injury, we hypothesize that the mitochondrial biogenesis regulatory program is an explicit target for cardiac therapeutic interventions. The objectives of this review are to (a) define the advances in understanding the mitochondrial biogenesis regulatory program integrated to its control of mitochondrial bioenergetics and oxygen utilization, (b) reveal how this program is modulated by chronic hypoxia and ischemic preconditioning, and (c) examine the therapeutic potential of modulating the regulation of mitochondrial biogenesis as a strategy to attenuate ischemia-reperfusion injury.
线粒体生物学研究的复兴源于这样一种认识，即线粒体为满足各种稳态需求而进行的独特调节是由精密的生化和分子控制机制驱动的。这个被称为线粒体生物发生的过程对于协调线粒体功能不可或缺，并且在生物力学和氧化应激后似乎会表现出适应性重塑。线粒体的主要生物能量功能将氧的最终利用分配在氧化磷酸化和活性氧之间。由于氧化磷酸化的破坏和过量的活性氧会导致心脏缺血再灌注损伤，我们推测线粒体生物发生调节程序是心脏治疗干预的一个明确靶点。本综述的目的是：（a）明确在理解整合了线粒体生物发生调节程序及其对线粒体生物能量学和氧利用控制方面取得的进展；（b）揭示该程序如何受到慢性缺氧和缺血预处理的调节；（c）研究调节线粒体生物发生的调控作为减轻缺血再灌注损伤策略的治疗潜力。
