Mitochondria in muscle cell death
Mitochondria in muscle cell death
复制标题
线粒体在肌肉细胞死亡中的作用
DOI：
--
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
P. Bernardi
中科院分区：
文献类型：
--
作者：
P. Bernardi
线粒体是真核细胞氧化磷酸化的主要能量来源，在细胞死亡途径中也起着关键作用。细胞死亡的模式可能受到ATP可用性的影响，其发生可能严重依赖于线粒体蛋白如细胞色素c、凋亡诱导因子和可能的半胱天冬酶3和9的释放。由亲环蛋白D调控的环孢素a敏感孔打开引起的Ca2+依赖性通透性转变，可能通过ATP耗损、Ca2+稳态破坏和特定线粒体蛋白的释放在细胞死亡中起主要作用。Ca2+稳态失调、蛋白水解和应对氧化应激能力下降与遗传病变下游Duchenne肌营养不良的发病机制有关，线粒体似乎是可能的靶点，可能会放大初始损伤，导致不可逆事件导致细胞死亡。我和我的同事正在研究骨骼肌线粒体的通透性转变，我们正在验证布比卡因在肌肉细胞毒性的短期模型中，包括线粒体去极化和孔打开作为早期事件。未来的具体目标是进一步确定线粒体在肌肉细胞死亡中的作用，特别强调通透性过渡孔和亲环蛋白D的作用，并在体外模型系统和杜氏肌营养不良动物模型mdx小鼠中开发和测试能够影响其过程的药物。
Abstract Mitochondria, the main source of energy for eukaryotic cells through oxidative phosphorylation, also play a key role in the pathways to cell death. The mode of cell death may be influenced by the availability of ATP, and its very occurrence may critically depend on release of mitochondrial proteins like cytochrome c, apoptosis-inducing factor and possibly caspases 3 and 9. Ca2+-dependent onset of the permeability transition, caused by opening of a cyclosporin A-sensitive pore modulated by cyclophilin D, may play a major role in cell death through ATP depletion, disruption of Ca2+ homeostasis, and release of specific mitochondrial proteins. Dysregulation of Ca2+ homeostasis, proteolysis and a decreased ability to cope with oxidative stress are involved in the pathogenesis of Duchenne's muscular dystrophy downstream of the genetic lesion, and mitochondria appear as likely targets that may amplify the initial insult resulting in the irreversible events leading to cell demise. My colleagues and I are studying the permeability transition in skeletal muscle mitochondria, and we are validating bupivacaine in a short-term model of muscle cell toxicity involving mitochondrial depolarization and pore opening as early events. Specific goals for the future are to further define the role of mitochondria in muscle cell death, with particular emphasis on the role of the permeability transition pore and cyclophilin D, and to develop and test drugs are able to affect its course in model systems in vitro and in the mdx mouse, an animal model of Duchenne's muscular dystrophy.
登录
查看更多内容
DOI：
10.1073/pnas.96.10.5752
发表时间：
1999-05-11
影响因子：
11.1
作者：
Krajewski, S;Krajewska, M;Reed, JC
通讯作者：
Reed, JC
影响因子：
56.9
作者：
Wang, HG;Pathan, N;Reed, JC
通讯作者：
Reed, JC
影响因子：
158.5
作者：
MENDELL, JR;KISSEL, JT;BURGHES, AHM
通讯作者：
BURGHES, AHM
影响因子：
4.4
作者：
Porter,JD;Edney,DP;McMahon,EJ;Burns,LA
通讯作者：
Burns,LA
DOI：
10.1016/s0005-2728(98)00124-8
发表时间：
1998-08
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Mauricio Montal
通讯作者：
Mauricio Montal