Ben-Shachar Dorit
Laboratory of Psychobiology, The Department of Psychiatry, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel.
J Neurochem. 2002 Dec;83(6):1241-51. doi: 10.1046/j.1471-4159.2002.01263.x.
Mitochondria are not only the principal source of high energy intermediates, but play an important role in intracellular calcium buffering, are main producers of reactive oxygen species, and are the source of pro- and antiapoptotic key factors. Moreover, the mitochondria are of a ubiquitous nature and the respiratory chain has a dual genetic basis, i.e. the mitochondrial and the nuclear DNAs. Thus mitochondrial impairment could provide an explanation for the tremendous heterogeneity of clinical and pathological manifestations in schizophrenia. This article reviews several independent lines of evidence that suggest an involvement of mitochondrial dysfunction in schizophrenia. Among them are altered cerebral energy metabolism, mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system and altered mitochondrial related gene expression. In addition, the interaction between dopamine, a predominant etiological factor in schizophrenia, and mitochondrial respiration is considered as a possible mechanism underlying the hyper- and hypo-activity cycling in schizophrenia. Understanding the role of mitochondria in schizophrenia may encourage novel treatment approaches, the identification of candidate genes and new insights into the pathophysiology and etiology of the disorder.
线粒体不仅是高能中间体的主要来源，而且在细胞内钙缓冲中起重要作用，是活性氧的主要产生者，也是促凋亡和抗凋亡关键因子的来源。此外，线粒体具有普遍存在的特性，呼吸链具有双重遗传基础，即线粒体DNA和核DNA。因此，线粒体损伤可以解释精神分裂症临床和病理表现的巨大异质性。本文综述了几条独立的证据线索，这些线索表明线粒体功能障碍与精神分裂症有关。其中包括大脑能量代谢改变、线粒体发育不全、氧化磷酸化系统功能障碍以及线粒体相关基因表达改变。此外，多巴胺作为精神分裂症的一个主要病因，与线粒体呼吸之间的相互作用被认为是精神分裂症中活动亢进和减退循环的一种可能机制。了解线粒体在精神分裂症中的作用可能会促进新的治疗方法的出现、候选基因的识别以及对该疾病病理生理学和病因学的新认识。
