Zhou Hao, Wang Shuyi, Hu Shunying, Chen Yundai, Ren Jun
Chinese People's Liberation Army General Hospital, People's Liberation Army Medical School, Beijing, China.
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY, United States.
Front Physiol. 2018 Jun 15;9:755. doi: 10.3389/fphys.2018.00755. eCollection 2018.
The mitochondrial and endoplasmic reticulum (ER) homeostasis is pivotal to the maintenance of an array of physiological processes. The physical contact and association between ER and mitochondria, known as the ER-mitochondria microdomains or mitochondria-associated ER membrane (MAM), temporally and spatially regulates the mitochondria/ER structure and function. More evidence suggests a role for MAMs in energy production, cellular contraction and mobility, and normal extracellular signal transmission. In pathological states, such as cardiac ischemia-reperfusion (I/R injury), this ER-mitochondria microdomains may act to participate in the cellular redox imbalance, ER stress, mitochondrial injury, energy deletion, and programmed cell death. From a therapeutic perspective, a better understanding of the cellular and molecular mechanisms of the pathogenic ER-mitochondria contact should help to identify potential therapeutic target for cardiac I/R injury and other cardiovascular diseases and also pave the road to new treatment modalities pertinent for the treatment of reperfusion damage in clinical practice. This review will mainly focus on the possible signaling pathways involved in the regulation of the ER-mitochondria contact. In particular, we will summarize the downstream signaling modalities influenced by ER-mitochondria microdomains, for example, mitochondrial fission, mitophagy, calcium balance, oxidative stress, and programmed cell death in details.
线粒体和内质网（ER）的稳态对于维持一系列生理过程至关重要。内质网与线粒体之间的物理接触和关联，即内质网-线粒体微结构域或线粒体相关内质网膜（MAM），在时间和空间上调节线粒体/内质网的结构和功能。更多证据表明MAM在能量产生、细胞收缩与移动以及正常细胞外信号传递中发挥作用。在病理状态下，如心脏缺血-再灌注（I/R损伤），这种内质网-线粒体微结构域可能参与细胞氧化还原失衡、内质网应激、线粒体损伤、能量缺失和程序性细胞死亡。从治疗角度来看，更好地理解致病性内质网-线粒体接触的细胞和分子机制应有助于确定心脏I/R损伤及其他心血管疾病的潜在治疗靶点，也为临床实践中治疗再灌注损伤的新治疗方式铺平道路。本综述将主要关注内质网-线粒体接触调节中可能涉及的信号通路。特别是，我们将详细总结受内质网-线粒体微结构域影响的下游信号模式，例如线粒体分裂、线粒体自噬、钙平衡、氧化应激和程序性细胞死亡。
