Context-dependent mitochondrial modulation of diastolic sarcoplasmic reticular calcium release.
Context-dependent mitochondrial modulation of diastolic sarcoplasmic reticular calcium release.
复制标题
舒张期肌浆网状钙释放的上下文依赖性线粒体调节。
DOI：
10.1093/cvr/cvac150
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发表时间：
2022
影响因子：
10.8
通讯作者：
Dorn,GeraldW
中科院分区：
文献类型：
--
作者：
Dorn,GeraldW
在阿尔伯特·冯·科利克发现线粒体165年后，线粒体因其无处不在的普遍性和特定背景下的功能多样性而继续挑战现代病理生理学概念。线粒体最初由理查德·奥尔特曼命名为“生物母细胞”，1898年从卡尔·本达那里获得了永久的名字，卡尔·本达将希腊语单词Mitos的意思是“线”和khondros的意思是“颗粒”结合在一起。80年后，1978年诺贝尔化学奖被授予彼得·D·米切尔，因为他提出了化学渗透假说，即氢离子在细胞膜上的传输产生了电化学势，将氧气消耗(呼吸作用)与三磷酸腺苷的产生联系起来。1近20年后(1997年)，诺贝尔委员会再次将线粒体研究化学奖授予保罗·D·博耶和约翰·E·沃克，以表彰他们阐明了ATP合成酶是如何从ADP和无机磷中生成ATP的。2线粒体通过氧化磷酸化产生ATP的中心作用赋予了这个独特的细胞器对细胞存活的基本功能，以及当ATP合成与呼吸分离时，通过阐述细胞毒性活性氧物种(ROS)来引发细胞损伤或破坏的能力。3线粒体机制是在线粒体通透性孔道持续转换后，通过caspase依赖的细胞凋亡或程序性坏死引起细胞程序性死亡。综上所述，这些特征表明线粒体是细胞健康和命运的关键仲裁者。除了产生三磷酸腺苷和触发细胞程序性死亡外，线粒体还因其输入、储存和释放钙的能力而被广泛认识。然而，线粒体钙信号的病理生理影响是不确定的，特别是在心肌细胞中，肌浆网(SR)的时相钙释放和重摄取介导兴奋收缩偶联。Tow等人。6通过询问临床前儿茶酚胺能多形性室性心动过速(CPVT)和糖尿病前期心肌病(Pre-DCM)小鼠模型中线粒体钙的输入和释放机制，增加了我们对线粒体钙信号和与SR的串扰的理解。他们报告了三个关键观察结果：
Over 165 years after their discovery by Albert von Kolliker, mitochondria continue to challenge modern pathophysiological concepts because of their ubiquity and context-specific functional diversity. First designated as ‘bioblasts’ by Richard Altman, mitochondria received their permanent name in 1898 from Carl Benda who combined the Greek word mitos meaning ‘thread’with khondros meaning ‘granule’. Eighty years later, the 1978 Nobel Prize for Chemistry was awarded to Peter D. Mitchell for advancing the chemiosmotic hypothesis that hydrogen ion trafficking across cell membranes created an electrochemical potential, linking oxygen consumption (respiration) to ATP production. 1 Almost 20 years thereafter (1997) the Nobel committee once more awarded a chemistry prize for mitochondrial research, to Paul D. Boyer and John E. Walker for elucidating how the enzyme ATP synthase creates ATP from ADP and inorganic phosphate. 2The central role played by mitochondria for ATP production via oxidative phosphorylation grants this unique organelle both an essential function for cell viability and, when ATP synthesis is uncoupled from respiration, the capacity to provoke cell damage or destruction via elaboration of cytotoxic reactive oxygen species (ROS). 3 Moreover, mitochondrial mechanisms evoke programmed cell death from caspase-dependent apoptosis or programmed necrosis after sustained transitioning of mitochondrial permeability pores. 4 Taken together, these features designate mitochondria as pivotal arbiters of cell fitness and fate. In addition to producing ATP and triggering programmed cell death, mitochondria are widely recognized for their ability to import, store, and release calcium. 5 However, the pathophysiological impact of mitochondrial calcium signalling is uncertain, particularly in cardiac myocytes wherein phasic sarcoplasmic reticular (SR) calcium release and re-uptake mediate excitation contraction coupling. Tow et al. 6 have increased our understanding of mitochondrial calcium signalling and crosstalk with SR by interrogating mitochondrial calcium import and release mechanisms in preclinical mouse models of catecholaminergic polymorphic ventricular tachycardia (CPVT) and pre-diabetic cardiomyopathy (pre-DCM). They report three key observations: