Norenberg M D, Rao K V Rama
Veterans Affairs Medical Center, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Neurochem Int. 2007 Jun;50(7-8):983-97. doi: 10.1016/j.neuint.2007.02.008. Epub 2007 Mar 4.
Mitochondria, being the principal source of cellular energy, are vital for cell life. Yet, ironically, they are also major mediators of cell death, either by necrosis or apoptosis. One means by which these adverse effects occur is through the mitochondrial permeability transition (mPT) whereby the inner mitochondrial membrane suddenly becomes excessively permeable to ions and other solutes, resulting in a collapse of the inner membrane potential, ultimately leading to energy failure and cell necrosis. The mPT may also bring about the release of various factors known to cause apoptotic cell death. The principal factors leading to the mPT are elevated levels of intracellular Ca2+ and oxidative stress. Characteristically, the mPT is inhibited by cyclosporin A. This article will briefly discuss the concept of the mPT, its molecular composition, its inducers and regulators, agents that influence its activity and describe the consequences of its induction. Lastly, we will review its potential contribution to acute neurological disorders, including ischemia, trauma, and toxic-metabolic conditions, as well as its role in chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
线粒体作为细胞能量的主要来源，对细胞生命至关重要。然而，具有讽刺意味的是，它们也是细胞死亡的主要介质，无论是通过坏死还是凋亡。这些不良反应发生的一种方式是通过线粒体通透性转换（mPT），即线粒体内膜突然对离子和其他溶质变得过度通透，导致内膜电位崩溃，最终导致能量衰竭和细胞坏死。mPT还可能导致各种已知会引起凋亡性细胞死亡的因子释放。导致mPT的主要因素是细胞内Ca2+水平升高和氧化应激。典型的是，mPT受环孢素A抑制。本文将简要讨论mPT的概念、其分子组成、诱导剂和调节剂、影响其活性的因素，并描述其诱导的后果。最后，我们将综述其对急性神经疾病（包括缺血、创伤和毒性代谢状况）的潜在影响，以及其在慢性神经退行性疾病（如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症）中的作用。
