PDF《线粒体呼吸链与活性氧》

(4) That ROS production by mitochondrial respiratory chain exhibited a non-linear dependence on ?ψ and was also controlled independently by both ?ψ and ?pH components of ?P, was described for first time by Liu and Huang in 1995-1997, and then experimentally re-confirmed by Skulachev'

s group in 1997-1998 and by Brand later in 2004. Presently, this finding of ?P (?ψ and ?pH) for controlling and regulating mitochondrial ROS generation in non-ohmic manner through affecting redox state and lifetime of ubisemiquinone at QO site of Q cycle has been commonly recognized among mitochondrial scientists as novel function of ?P in addition to its traditional role in energy transduction for ATP synthesis. Therefore, it is emphasized that mitochondria, more than just a powerhouse, are an integral part of multiple cell signaling cascades linking mitochondrial function and dynamics to the regulation of diverse cellular events, including gene regulation, metabolism, development, cell differentiation, senescence and cell death. Also, the theoretical basis of Mitchell'

s Chemiosmotic theory could be involved not only in energy transduction and ions translocation of energy tranducing membrane system including mitochondria, as described originally by Mitchell(1961-66), but also spread to affect cellular redox signaling through its controlling mechanism for mitochondrial ROS production. Key words:mitochondrial respiratory chain;

ubisemiquinone in Q0 site of Q cycle;

non-ohmic dependence of ROS generation on ?P;

control of ROS by ?ψ and ?pH;

partition and across membranes of ROS;

Cyt c-p66Shc redox protein;

novel function of ?P

521 第4期刘树森:线粒体呼吸链与活性氧 reductase、monoamine oxidases、dihydroorotate dehydrogenase等.但所有这些酶活及ROS产生量都 远低于线粒体内膜呼吸链酶系.人体线粒体内膜面 积达

14 000m2 ,呼吸链酶复合体是其主要组份;

一 成年人每天吸氧 400L,通过呼吸链将 O2 还原为 H2O.如果按 in vivo 耗氧的 0.1% 以呼吸链 电子 漏(electron leak) 的单电子还原生成 O2 - ・,则日产 量可达 400mL 之巨,超出所有其他酶活性之总和[8] . 本文讨论线粒体 ROS 问题也以线粒体呼吸链为 中心.

2 线粒体呼吸链 ROS的生成位点问题 生理条件下, 生物吸收的O2主要在线粒体呼吸 链末端氧化酶(复合体 IV)的作用下还原成 H2O.由于O2 在基态时的三重态构象, 分子外层具两未成对 电子,因此 O2 还原为 H2O 是通过连续接受

4 个单电 子的

4 步还原来完成.线粒体的呼吸链电子传递全 程由电子传递链复合体 I、II、III 和IV 的共同作 用完成,泛醌(Q)在复合体 I 和III 或II 和III 之间, 细胞色素C在复合体III和IV之间传递电子. Boveris 和Chance (1973)首次报道,离体肝和心脏线粒体呼 吸产生 O2 - ・量相当于耗氧的 1% - 2%,从线粒体扩 散到细胞浆中的 H2O2 也是来源于 O2 - ・的氧化,两者 呈化学计量关系.他们早期研究得到多数实验室的 支持[6,9,10] .近来,虽有报到,在生理条件下生物 体内线粒体ROS生成仅为耗氧的0.2%, 或者如Nohl 等坚持认为,线粒体复合体 I 不是 O2 - ・和H2O2 有效 来源,而是复合体 III[11] .但从离体线粒体研究证 明,呼吸链复合体 I 或III 中途的 电子漏 使氧 可直接接受单电子生成 O2 - ・ [5] .在呼吸链活性受阻、 机体应激、衰老或疾病造成线粒体呼吸链损伤时, ROS 生成量进一步增加和积聚,引起氧化损伤.在 线粒体基质中 O