Regulation of Mitochondrial ATP Production: Ca(2+) Signaling and Quality Control.

Regulation of Mitochondrial ATP Production: Ca(2+) Signaling and Quality Control.
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DOI:
10.1016/j.molmed.2019.10.007
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发表时间:
2020-01
影响因子:
13.6
通讯作者:
Lederer WJ
Lederer WJ
中科院分区:
医学1区
文献类型:
--
作者:
Boyman L;Karbowski M;Lederer WJ

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心脏ATP的产生主要依赖于线粒体中的氧化磷酸化,并受线粒体基质中的Ca2+水平以及胞质ADP的动态调节。在这里,我们讨论线粒体Ca2+信号及其功能障碍,最近已被链接到心脏病理,包括心律失常,心力衰竭。其他可兴奋和长寿细胞(如神经元)的类似功能障碍与神经退行性疾病(如阿尔茨海默病,ALS和帕金森病)有关。这一新认识的核心是Ca2+对线粒体质量控制和ATP产生的关键调节。线粒体相关膜(MAM)信号从肌质和内质网线粒体进行了讨论。我们提出了未来的研究方向,强调需要定量定义MAMs的生理作用,以及线粒体的质量控制和ATP的生产。
Cardiac ATP production primarily depends on oxidative phosphorylation in mitochondria and is dynamically regulated by Ca2+ levels in the mitochondrial matrix as well as cytosolic ADP. Here we discuss mitochondrial Ca2+ signaling and its dysfunction which has recently been linked to cardiac pathology including arrhythmia, and heart failure. Similar dysfunction in other excitable and long-lived cells like neurons is associated with neurodegenerative diseases such as Alzheimer’s disease, ALS and Parkinson’s disease. Central to this new understanding is the critical regulation by Ca2+ of both mitochondrial quality control and ATP production. Mitochondrial associated membrane (MAM) signaling from sarcoplasmic and endoplasmic reticulum to mitochondria is discussed. We propose future research directions that emphasize a need to define quantitatively the physiological roles of MAMs, and both mitochondrial quality control and ATP production.
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