Polyzos Aris A, McMurray Cynthia T
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd., Berkeley, CA 94720, USA.
Mech Ageing Dev. 2017 Jan;161(Pt A):181-197. doi: 10.1016/j.mad.2016.09.003. Epub 2016 Sep 12.
Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington's disease, Alzheimer's disease, and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell. The effects of these various parameters are difficult to quantify and not fully understood, but clearly have an impact on interpreting the bioenergetics of MT or their failure in disease states. A major goal of the review is to discuss issues and coalesce detailed information into a reference table to help in assessing mitochondrial dysfunction as a cause or consequence of Huntington's disease.
线粒体功能障碍及随之而来的氧化损伤通常被认为是亨廷顿舞蹈症、阿尔茨海默病和帕金森病的主要病因。毫无疑问,随着神经元死亡,线粒体(MT)会出现缺陷,但MT缺陷是主要病因还是毒性的有害后果仍未得到解答。氧消耗率(OCR)和糖酵解为MT的功能状态和细胞代谢调节提供了敏感且信息丰富的指标,然而这些指标会因样本来源不同而有所差异;包括物种、组织类型、测量时的年龄,以及MT是在纯化形式下还是在细胞中进行测量。这些不同参数的影响难以量化且尚未完全理解,但显然会对解释MT的生物能量学或其在疾病状态下的功能衰竭产生影响。本综述的一个主要目标是讨论相关问题,并将详细信息汇总成一个参考表,以帮助评估线粒体功能障碍是亨廷顿舞蹈症的病因还是后果。