线粒体 ATP 生成的调节：钙信号和质量控制。
Regulation of Mitochondrial ATP Production: Ca Signaling and Quality Control.
机构信息
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
出版信息
Trends Mol Med. 2020 Jan;26(1):21-39. doi: 10.1016/j.molmed.2019.10.007. Epub 2019 Nov 22.
Cardiac ATP production primarily depends on oxidative phosphorylation in mitochondria and is dynamically regulated by Ca levels in the mitochondrial matrix as well as by cytosolic ADP. We discuss mitochondrial Ca signaling and its dysfunction which has recently been linked to cardiac pathologies including arrhythmia and heart failure. Similar dysfunction in other excitable and long-lived cells including neurons is associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Central to this new understanding is crucial Ca regulation of both mitochondrial quality control and ATP production. Mitochondria-associated membrane (MAM) signaling from the sarcoplasmic reticulum (SR) and the endoplasmic reticulum (ER) to mitochondria is discussed. We propose future research directions that emphasize a need to define quantitatively the physiological roles of MAMs, as well as mitochondrial quality control and ATP production.
心脏的 ATP 生成主要依赖于线粒体中的氧化磷酸化，并且受到线粒体基质中 Ca 水平和胞质 ADP 的动态调节。我们讨论了线粒体 Ca 信号及其功能障碍，最近已将其与包括心律失常和心力衰竭在内的心脏病理联系起来。其他兴奋性和长寿细胞（包括神经元）中的类似功能障碍与神经退行性疾病（如阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）和帕金森病（PD））有关。这一新认识的核心是 Ca 对线粒体质量控制和 ATP 生成的关键调节。讨论了来自肌浆网（SR）和内质网（ER）到线粒体的线粒体相关膜（MAM）信号。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，以及线粒体质量控制和 ATP 生成。
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