Rose Jordan, Brian Christian, Woods Jade, Pappa Aglaia, Panayiotidis Mihalis I, Powers Robert, Franco Rodrigo
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68588, United States; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
Toxicology. 2017 Nov 1;391:109-115. doi: 10.1016/j.tox.2017.06.011. Epub 2017 Jun 26.
Mitochondrial dysfunction is central to the pathogenesis of neurological disorders. Neurons rely on oxidative phosphorylation to meet their energy requirements and thus alterations in mitochondrial function are linked to energy failure and neuronal cell death. Furthermore, in neurons, dysfunctional mitochondria are reported to increase the steady-state levels of reactive oxygen species derived from the leakage of electrons from the electron transport chain. Research aimed at understanding mitochondrial dysfunction and its role in neurological disorders has been primarily geared towards neurons. In contrast, the effects of mitochondrial dysfunction in glial cells' function and its implication for neuronal homeostasis and brain function has been largely understudied. Unlike neurons and oligodendrocytes, astrocytes and microglia do not degenerate upon the impairment of mitochondrial function, as they rely primarily on glycolysis to produce energy and have a higher antioxidant capacity than neurons. However, recent evidence highlights the role of mitochondrial metabolism and signaling in glial cell function. In this work, we review the functional role of mitochondria in glial cells and the evidence regarding its potential role regulating neuronal homeostasis and disease progression.
线粒体功能障碍是神经疾病发病机制的核心。神经元依靠氧化磷酸化来满足其能量需求,因此线粒体功能的改变与能量衰竭和神经元细胞死亡有关。此外,据报道,在神经元中,功能失调的线粒体可增加因电子从电子传递链泄漏而产生的活性氧的稳态水平。旨在了解线粒体功能障碍及其在神经疾病中作用的研究主要针对神经元。相比之下,线粒体功能障碍对胶质细胞功能的影响及其对神经元内环境稳定和脑功能的影响在很大程度上尚未得到充分研究。与神经元和少突胶质细胞不同,星形胶质细胞和小胶质细胞在线粒体功能受损时不会退化,因为它们主要依靠糖酵解来产生能量,并且比神经元具有更高的抗氧化能力。然而,最近的证据突出了线粒体代谢和信号传导在胶质细胞功能中的作用。在这项工作中,我们综述了线粒体在胶质细胞中的功能作用以及关于其调节神经元内环境稳定和疾病进展潜在作用的证据。