Rustin P, von Kleist-Retzow J C, Vajo Z, Rotig A, Munnich A
Medical Genetics Service, INSERM U393, Hospital Necker, 149, rue de Sevres, 75743, Paris, France.
Mech Ageing Dev. 2000 Apr 14;114(3):201-6. doi: 10.1016/s0047-6374(00)00102-0.
As both experimental evidence and theoretical considerations may suggest that free radicals and mitochondria might be associated as key factors in aging, these organelles have been implicated in various versions of the free radical theory of aging. However, except for a few cases, no evidence for a death process specifically activated in respiratory defective cells could be found in patients with a mitochondrial disorder, including those harboring high levels of mutant mtDNA associated with profound respiratory chain deficiencies. This and more recent evidence suggest that damages produced by free-radicals endogenously generated in the mitochondria result in a distinctive biochemical profile, only occur under exceptional conditions and that a dysfunction of the respiratory chain does not cause opening of the permeability transition pore and is not sufficient per se to trigger massive entrance of cells into death processes, neither apoptosis nor necrosis. Therefore, defective mitochondria and their particular genome, should not be considered as a major and primary source of free radicals either leading cells into a death cascade or resulting in an accelerated aging process.
由于实验证据和理论思考均表明自由基和线粒体可能是衰老的关键相关因素，这些细胞器已被纳入各种版本的衰老自由基理论中。然而，除了少数情况外，在线粒体疾病患者中，包括那些携带与严重呼吸链缺陷相关的高水平突变线粒体DNA的患者，未发现有证据表明呼吸缺陷细胞中存在特异性激活的死亡过程。这一发现以及最近的证据表明，线粒体中内源性产生的自由基所造成的损伤会导致独特的生化特征，且仅在特殊情况下才会出现，呼吸链功能障碍不会导致通透性转换孔开放，其本身也不足以触发细胞大量进入死亡过程，无论是凋亡还是坏死。因此，有缺陷的线粒体及其特定基因组，不应被视为导致细胞进入死亡级联反应或加速衰老过程的自由基的主要和原始来源。
