间断性阻断肝血流对肝细胞和线粒体的保护作用

本实验观察并评价间断性和持续性肝缺血再灌注对大鼠肝细胞和线粒体结构功能、肝组织内钙和脂质过氧化物(LPO)含量．以及超氧化物歧化酶(SOD)活性改变的影响。实验大鼠分为持续阻断组、间断阻断和假处理组。结果表明；持续性缺血再灌注后大鼠肝线粒体呼吸控制比率，磷氧比值和氧化磷酸化效率均显著降低，肝组织内钙和LPO含量均增高，SOD活性下降，细胞损伤较重。间断性缺血再灌注后，上述指标无明显异常改变，细胞损伤较轻。说明间断性肝缺血有利于保护肝细胞和线粒体功能，该效应与细胞内钙稳定和SOD活性增高有关。     

局灶性缺血再灌注大鼠脑线粒体损伤的实验研究

采用大鼠大脑中动脉缺血（MCAO）再灌注模型，观察缺血再灌注不同时相（分为五组）脑线粒体损伤的变化规律。结果为脑缺血再灌注后线粒体基质游离钙含量（MCa）明显高于假手术组Na^＋、K^＋-ATP酶、Ca^2＋、Mg^＋-ATP酶活性明显下降，且随时间的延长下降明显；再灌注0．5h的MDA和SOD均元明显变化，再灌注1h后线粒体MDA含量明显升高，SOD活性明显下降。说明脑缺血再灌注线粒体损伤与线粒体钙超载及线粒体内膜氧化磷酸化有关。     

纳洛酮对缺血再灌注海马细胞线粒体功能保护作用的研究

目的观察缺血再灌注期间海马细胞内游离钙离子、线粒体膜电位的变化以及纳洛酮对细胞的保护作用。方法20只新西兰大白兔随机分成4组对照组、缺血组、再灌注组、纳洛酮组,每组5只,然后以荧光染色流式细胞仪检测各实验组海马细胞内游离钙离子浓度和线粒体膜电位的变化。结果缺血组、再灌注组海马细胞内游离钙离子浓度显著高于对照组和纳洛酮组;其线粒体膜电位则低于对照组和纳洛酮组;再灌注组游离钙离子浓度明显高于缺血组;其线粒体膜电位则低于缺血组;对照组与纳洛酮组间各指标无显著差异。结论纳洛酮对缺血再灌注引起的海马细胞内钙离子浓度升高有抑制作用,对线粒体膜电位下降有一定的保护作用。     

褪黑素对脑缺血后线粒体的影响

目的 探讨褪黑素对脑缺血后脑细胞线粒体的保护作用及其机制。方法采用蒙古沙土鼠全脑缺血再灌注模型,在沙土鼠双侧颈动脉夹闭前腹腔内注射褪黑素,制备药物治疗模型。对照组以生理盐水代替褪黑素。分离前脑线粒体,测定线粒体三磷酸腺苷酶(ATP酶)活力、线粒体内游离钙水平、线粒体内还原型谷胱甘肽(GSH)含量等指标．结果(1)缺血组脑线粒体GSH水平明显降低,与药物治疗组和对照组之间存在显差异,而对照组和药物治疗纽比较,差异无显性意义;(2)缺血后ld和3d纽脑线粒体内钙超载,与对照纽和药物治疗纽比较差异显,而对照组和药物治疗组比较,差异无显性意义;(3)缺血组脑线粒体Na^ ,K^ -ATP酶和ca^ ,Mg^2 -ArrP酶活力与对照组和药物治疗组相比明显降低,且随着缺血时间的延长而递降。结论褪黑素可以提高脑线粒体对缺血、缺氧的耐受性,维持脑细胞线粒体结构和功能的稳态,保护缺血后的脑细胞。褪黑素对缺血后再灌注的脑神经元有保护作用．可能是通过保护线粒体这一环节来实现的．     

曲美他嗪对大鼠缺血再灌注心肌线粒体的保护作用

目的探讨曲美他嗪对缺血再灌注损伤心肌线粒体的保护作用及其机制.方法将50只SD雄性大鼠随机分为假手术组、生理盐水组和曲美他嗪组(5mg/kg组及10mg/kg组)4组,假手术组只开胸,不结扎冠状动脉.余3组复制缺血再灌注损伤模型,缺血前分别静脉注射曲美他嗪(5或10mg/kg)及等量生理盐水,在缺血30min及再灌注40min时测定缺血再灌注损伤区心肌线粒体丙二醛、超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶及总钙浓度,并通过电镜观察心肌超微结构的改变.结果与假手术组比较,生理盐水组及曲美他嗪组线粒体中的丙二醛及总钙显著增高,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著降低.与生理盐水组比较,曲美他嗪组的丙二醛及总钙水平显著降低,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著增高.电镜观察显示曲美他嗪组线粒体损伤较生理盐水组明显减轻.结论以上提示曲美他嗪能减轻缺血再灌注心肌线粒体的脂质过氧化损伤,其机制可能是通过提高线粒体内谷胱甘肽含量及超氧化物歧化酶和谷胱甘肽过氧化物醇活性,以增强其抗氧化能力,并通过减轻线粒体内钙聚积在细胞水平提供心肌保护作用.     

姜黄素对缺血再灌注损伤大鼠心肌线粒体呼吸链的影响

目的 探讨姜黄素对心肌缺血再灌注损伤大鼠心肌梗死面积及心肌线粒体呼吸链的影响。方法 采用健康雄性Wister大鼠（n=24）建立Langendorff离体心脏灌注模型,分为3组,正常对照组、缺血再灌注组和姜黄素预处理组。正常对照组持续灌注90 min;缺血再灌注组全心缺血30 min,再灌注60 min;姜黄素预处理组加入姜黄素（0.2 mmol/L）后,全心缺血30 min,再灌注60 min。再灌注结束时,TTC染色观察心肌梗死面积,应用紫外分光光度法测定缺血再灌注后心肌线粒体呼吸链复合体Ⅰ、Ⅳ的活性。结果[结果部分应列举主要数据,并修改英文摘要] ①缺血再灌注组心肌坏死面积约为26.9±2.5%。经姜黄素预处理后,心肌梗死面积为21.8±2.2%,较缺血再灌注组明显降低,差异有统计学意义;②缺血再灌注组心肌线粒体呼吸链复合体Ⅰ、Ⅳ活性分别为0.453±0.069、0.050±0.005,姜黄素预处理组心肌线粒体呼吸链复合体Ⅰ、Ⅳ活性分别为0.565±0.071、0.059±0.004,较缺血再灌注组均显著增加,差异有统计学意义（P<0.05）。结论 姜黄素预处理能够缩小心肌梗死面积,同时增加线粒体呼吸链复合体Ⅰ、Ⅳ的活性,从而对缺血再灌注损伤心肌起保护作用。     

辛伐他汀对大鼠局灶性脑缺血的线粒体保护作用

目的：探讨辛伐他汀对局部脑缺血损伤大鼠的保护作用及其线粒体机制。方法：96只大鼠随机分为假手术组、缺血再灌注组和辛伐他汀处理组，每组32只。建立大鼠大脑中动脉闭塞（MCAO）模型，观察大鼠神经功能、梗死体积、脑组织线粒体超微结构的改变；检测线粒体细胞色素c氧化酶（COX）、琥珀酸脱氢酶（SDH）活性，Ca^2＋含量，以及血清降钙素基因相关肽（CGRP）含量。结果：与假手术组相比较，缺血再灌注组各项指标均有显著改变；与缺血再灌注组比较，辛伐他汀能明显提高脑缺血大鼠的神经功能评分（P〈0．01），缩小梗死体积（P〈0．01），改善脑组织线粒体结构，并提高脑组织线粒体SDH活性（P〈0．05），提高COX活性（P〈0．01），降低脑组织线粒体Ca^2＋的含量（P〈0．01），提高血清CGRP水平（P〈0．05）。结论：辛伐他汀可能通过其抗氧化效应，提高脑组织线粒体SDH、COX活性及血清CGRP水平，减轻钙超载，缩小梗死体积，改善神经功能，从而对大鼠局灶性脑缺血起保护作用。     

脑缺血再灌注损伤引起的线粒体功能障碍及丹参酮ⅡA的保护作用研究

目的探讨丹参酮ⅡA(TanⅡA)对缺血再灌注损伤大鼠缺血皮质线粒体的保护作用。方法将SD大鼠随机分为假手术组、缺血再灌注组、TanⅡA低、中、高剂量治疗组,线栓法建立局灶性脑缺血再灌注模型。TanⅡA高、中、低剂量治疗组于术前连续灌胃给予高、中、低剂量TanⅡA 7d,1次/d。采用C lark-氧电极检测线粒体呼吸功能,同时采用荧光分光光度计检测线粒体氧自由基的含量。采用生化方法检测线粒体呼吸链酶复合物活性,以及线粒体肿胀度。处死前,进行神经行为学评分。结果脑缺血再灌注24h,缺血再灌注组线粒体功能明显受损,丹参酮ⅡA能够改善线粒体功能。结论 TanⅡA对缺血再灌注线粒体损伤具有保护作用,可能与清除氧自由基有关。     

依达拉奉对断肢再植后缺血再灌注损伤大鼠骨骼肌线粒体的保护作用及机制

目的探讨依达拉奉对断肢再植后缺血再灌注损伤大鼠骨骼肌线粒体的保护作用及其机制。方法36只成年Wistar大鼠，随机分为对照组、冷冻组和药物组。对照组只暴露股动、静脉，不离断肢体；余两组制作深低温保存断肢再植缺血再灌注损伤动物模型，药物组洗脱液中含依达拉奉0．5mg／kg。选取相同时点骨骼肌标本，提取骨骼肌线粒体，测定线粒体丙二醛（MDA）、超氧化物歧化酶（SOD）、线粒体呼吸控制率及抗氰呼吸，并对骨骼肌线粒体超微结构行透射电镜观察。结果与对照组相比，冷冻组与药物组线粒体中的MDA显著增高，抗氰呼吸显著增加，SOD显著降低，呼吸控制率显著下降。与冷冻组比较，药物组的MDA水平及抗氰呼吸显著降低，SOD显著增高，呼吸控制率显著升高（P均〈0．05）；病理改变在冷冻组最为严重，药物组再灌注骨骼肌大部分线粒体完整。结论依达拉奉能减轻深低温保存大鼠断肢再植骨骼肌线粒体的缺血再灌注损伤。其可能与依达拉奉直接抑制羟自由基，提高骨骼肌线粒体内SOD活性，减少MDA的产生，使细胞进行正常的氧化磷酸化有关。     

三七总皂苷保护海马区神经元线粒体膜电位的实验研究

目的 研究三七总皂苷对缺血再灌注后海马区神经元线粒体膜电位的保护作用.方法 36只SD大鼠随机分为假手术组、模型组、三七总皂苷组,每组12只.建立大鼠脑缺血再灌注模型,荧光染色流式细胞仪检测各组海马区神经元内游离Ca2+浓度和线粒体膜电位的变化.结果 与假手术组比较,模型组海马区神经元内游离Ca2+浓度明显升高,线粒体膜电位明显降低(P＜0.01);与模型组比较,三七总皂苷组海马区神经元内游离Ca2+浓度明显降低(P＜0.01),线粒体膜电位明显升高(P＜0.05).结论 三七总皂苷能抑制缺血再灌注引起的海马区神经元内Ca2+浓度升高,抑制线粒体膜电位下降,保护海马区神经元线粒体功能,这可能是其抗脑缺血再灌注损伤的作用机制之一.     

Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning

AIM: To investigate the role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning (IPC). METHODS: A rat model of acute hepatic ischemia-reperfusion was established, 24 healthy male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group. IPC was achieved by several brief pre-reperfusions followed by a persistent reperfusion. Concentration of malondialdehyde (MDA) and activity of several antioxidant enzymes in hepatic tissue were measured respectively. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and expression of Bcl-2 protein was measured by immunohistochemical techniques. Moreover, mitochondrial ultrastructure and parameters of morphology of the above groups were observed by electron microscope. RESULTS: Compared with IR group, the concentration of MDA and the hepatocellular apoptotic index in IPC group was significantly reduced (P<0.05), while the activity of antioxidant enzymes and OD value of Bcl-2 protein were markedly enhanced (P<0.05). Moreover, the injury of mitochondrial ultrastructure in IPC group was also obviously relieved. CONCLUSION: IPC can depress the synthesis of oxygen free radicals to protect the mitochondrial ultrastructure and increase the expression of Bcl-2 protein that lies across the mitochondrial membrane. Consequently, IPC can reduce hepatocellular apoptosis after reperfusion and has a protective effect on hepatic ischemia-reperfusion injury.     

Effect of superoxide generation on rat heart mitochondrial pyruvate utilization

Previous research has shown that heart mitochondria are able to produce reactive species of oxygen such as superoxide radicals, hydrogen peroxide and hydroxyl radicals [10, 11]. When these compounds are formed beyond a certain level they are not completely removed by the enzymatic and metabolic processes which neutralize their toxicity, and as a result they are able to produce structural and functional damages that impair mitochondrial function [5, 10]. In order to study the molecular mechanism/s by which the oxygen radicals may function as mediators of cellular injury a flow of these radicals by chemical, enzymatic or photochemical methods has been generated in vitro in the presence of cellular preparations. For example, the exposure of isolated subcellular particles to the enzymatic flow of oxygen radicals produced by the reaction of xanthine oxidase upon xanthine reduced both calcium uptake velocity and Ca2+-ATPase activity in sarcoplasmic reticulum [7], while it reduced Ca2+-stimulated ATPase activity in myofibrillar preparations [4]. In addition, incubation with the xanthine oxidase reaction produced an impairment of the respiratory functions associated with an increased lipid peroxidation in the isolated mitochondria [5, 10]. These negative effects were augmented in alpha-tocopherol-deficient mitochondria [3], but were opposed by the exogenous addition of superoxide dismutase [10]. This report shows that the superoxide radicals generated by the xanthine oxidase reaction reduced rat heart mitochondrial respiration induced by pyruvate. This negative effect was partially prevented by superoxide dismutase and catalase and by thiol protecting agents. Moreover, the generation of free radicals caused a significant reduction in the rate of (1-14C) -pyruvate decarboxylation, while it did not change the transport of pyruvate into mitochondria.     

钙和氧自由基在急性心肌梗死时线粒体膜介导的细胞死亡途径中的作用

在急性心肌梗死时,过量产生的活性氧和细胞内钙积聚对启动程序性细胞死亡起重要作用。细胞死亡包括坏死、凋亡、自噬及其共同作用。在缺血过程中,肌浆网、肌丝之间的钙处理被中断,同时钙转移至线粒体导致其肿胀,再灌注激活能量传导和心肌收缩导致氧自由基释放及其他离子失衡,在急性缺血一再灌注过程中,主要的死亡途径是线粒体通透性转换孔开放和线粒体外膜通透性增加启动内源性程序性坏死和凋亡。尽管国内外学者做了深入的研究,但调节线粒体膜通透性的作用和机制尚未完全了解。外源性凋亡、坏死性凋亡和自噬也可能加重缺血一再灌注所致的损伤。在这篇综述中,我们将讨论心肌梗死时钙失调和氧自由基、Bcl一2蛋白、线粒体膜通透性改变在心肌细胞死亡途径中的作用。     

缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用

目的　探讨缺血后处理对肝脏缺血再灌注中肝窦内皮细胞损伤的保护作用。方法　建立大鼠局部肝脏缺血再灌注模型 ,将 2 4只健康雄性Wistar大鼠随机分为假手术、缺血再灌注、缺血后处理 3组 ,以缺血再灌前、反复多次的短暂预再灌、停灌作后处理 ,观察各组血浆肝酶及透明质酸 (HA)水平变化和肝组织中丙二醛 (MDA)、超氧化物歧化酶(SOD)、内皮素 1(ET 1)含量 ,并行肝组织病理形态学检查。结果　与缺血再灌注组相比 ,缺血后处理组肝酶的漏出、血浆HA水平及肝组织中MDA、ET 1的含量明显降低 (P <0 .0 1) ,而SOD活性则显著升高 (P <0 .0 1) ,肝组织病理学损伤亦明显减轻。结论　缺血后处理可通过抑制再灌注后氧自由基的过量生成而保护肝窦内皮细胞 ,减轻肝脏缺血再灌注损伤。     

Impact of acute ischemia-reperfusion on myocardial mitochondrial function in an ex-vivo model of global myocardial ischemia.

INTRODUCTION: Cardiac mitochondria, as the major source of energy used by the heart, play an important part in the survival of cardiomyocytes undergoing ischemia followed by reperfusion. During ischemia, cardiac mitochondria represent one of the main cellular defense mechanisms, acting as a calcium-sequestering system and maintaining levels of energy production. However, when these cellular mechanisms are overcome, loss of mitochondrial integrity leads not only to the breakdown of energy production, but also to the release of pro-apoptotic factors, thus compromising the survival of cardiac cells. OBJECTIVES: To study the impact of acute ischemia-reperfusion (IR) on myocardial mitochondrial function in an ex-vivo model of global ischemia. METHODS: Wistar rat hearts were divided into two groups: control (165 minutes of perfusion with Krebs-Henseleit solution) and ischemia-reperfusion (IR - 10 minutes perfusion, followed by 35 minutes ischemia and 120 minutes reperfusion). Various parameters of mitochondrial function were assessed: respiratory control ratio (RCR) using a Clark-type oxygen electrode, oxidative stress (using the thiobarbituric acid reactive substances [TBARS] test), and mitochondrial swelling amplitude and calcium uptake, both determined by fluorimetric methods. RESULTS: All mitochondrial parameters were severely affected by IR. The IR group showed a significant decrease in RCR, which was independent of the respiratory substrate used, for each assay. There were no significant differences between the two experimental groups in TBARS production. The control group showed a trend for a decrease in mitochondrial swelling amplitude and an increase in calcium uptake compared to the IR group, in both the absence and presence of cyclosporin A. CONCLUSIONS: In this study, IR significantly altered mitochondrial function (RCR, mitochondrial swelling amplitude and intramitochondrial calcium uptake). This means that during acute myocardial ischemia, every effort should be made to avoid reperfusion injury, given its deleterious consequences for coronary artery disease patients.     

Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion

We assessed the effects of melatonin, a powerful scavenger of oxygen free radicals, on ischemia/reperfusion-induced oxidative damage to mitochondria in the rat placenta. In Wistar rats at day 19 of pregnancy, feto-placental ischemia was induced by occluding both utero-ovarian arteries for 20 min. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. Melatonin solution or the vehicle alone was injected intraperitoneally at dose of 10 mg/kg 1 hr before occlusion. Sham-ischemic animals were treated with vehicle. Each group consisted of 10 pregnant rats. We measured placental mitochondrial respiratory control index (RCI; a marker of mitochondrial respiratory activity), the ratio of the added adenosine 5-diphosphate (ADP) concentration to consumption of oxygen during state 3 respiration (ADP/O), and the concentration of thiobarbituric acid reactive substances (TBARS) in each group. RCI and ADP/O were significantly decreased by ischemia/reperfusion, while TBARS were increased. Melatonin prevented these changes. These results indicate that exogenous melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placenta. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excess free radical production, such as fetal growth restriction and fetal hypoxia.     

Impact of carvedilol on the mitochondrial damage induced by hypoxanthine and xantine oxidase--what role in myocardial ischemia and reperfusion?

OBJECTIVES: The cardioprotective effects of carvedilol (CV) may be explained in part by interactions with heart mitochondria. The objective of this work was to study the protection afforded by CV against oxidative stress induced in isolated heart mitochondria by hypoxanthine and xanthine oxidase (HX/XO), a well-known source of reactive oxygen species (ROS) in the cardiovascular system. METHODS: Mitochondria were isolated from Wistar rat hearts (n = 8) and incubated with HX/XO in the presence and in the absence of calcium. Several methods were used to assess the protection afforded by CV: evaluation of mitochondrial volume changes (by measuring changes in the optical density of the mitochondrial suspension), calcium uptake and release (with a fluorescent probe, Calcium Green 5-N) and mitochondrial respiration (with a Clark-type oxygen electrode). RESULTS: CV decreased mitochondrial damage associated with ROS production by HX and XO, as verified by the reduction of mitochondrial swelling and increase in mitochondrial calcium uptake. In the presence of HX and XO, CV also ameliorated mitochondrial respiration in the active phosphorylation state and prevented decrease in the respiratory control ratio (p < 0.05) and in mitochondrial phosphorylative efficiency (p < 0.001). CONCLUSIONS: The data indicate that CV partly protected heart mitochondria from oxidative damage induced by HX and XO, which may be useful during myocardial ischemia and reperfusion. It is also suggested that mitochondria may be a priority target for the protective action of some compounds.     

Mitochondrial diabetes mellitus

This review discusses the current insight by which mutations in mitochondrial DNA (mtDNA) contribute to the development of particular disease states with emphasis on diabetes mellitus. Mitochondria are the power factories of the cells and produce ATP by oxidizing reducing equivalents via the respiratory chain. These reducing equivalents originate mainly from the citric acid cycle that also occurs within the mitochondria. Human mitochondria contain their own genetic material in the form of circular DNA that encodes for only a fraction of the mitochondrial components. The other mitochondrial components are nuclear encoded. Pathogenic mutations in mtDNA can affect the activity of the respiratory chain, thereby leading to the reduced generation of ATP. However, mitochondria not only produce ATP but they also regulate cytosolic concentrations of signaling molecules such as calcium and iron ions. The metabolic processes within mitochondria such as the citric acid cycle determine the concentration of metabolites that can also act as signalling molecules. Furthermore, the respiratory chain and mitochondrion-associated monoamine oxidase are major producers of reactive oxygen radicals. As a result, mutations in mtDNA can deregulate multiple processes within cells and the balance of this deregulation may contribute to the clinical phenotype.     

Oxidative and nitrosative stress in brain mitochondria of diabetic rats

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.     

Hypersensitivity to oxygen and shortened lifespan in a Drosophila mitochondrial complex II mutant

Oxidative stress is implicated as a major cause of aging and age-related diseases, such as Parkinson's and Alzheimer's, as well as ischemia-reperfusion injury in stroke. The mitochondrial electron transport chain is the principal source of reactive oxygen species within cells. Despite considerable medical interest, the molecular mechanisms that regulate reactive oxygen species formation within the mitochondrion remain poorly understood. Here, we report the isolation and characterization of a Drosophila mutant with a defect in subunit b of succinate dehydrogenase (SDH; mitochondrial complex II). The sdhB mutant is hypersensitive to oxygen and displays hallmarks of a progeroid syndrome, including early-onset mortality and age-related behavioral decay. Pathological analysis of the flight muscle, which is amongst the most highly energetic tissues in the animal kingdom, reveals structural abnormalities in the mitochondria. Biochemical analysis shows that, in the mutant, there is a complex II-specific respiratory defect and impaired complex II-mediated electron transport, although the other respiratory complexes remain functionally intact. The complex II defect is associated with an increased level of mitochondrial hydrogen peroxide production, suggesting a possible mechanism for the observed sensitivity to elevated oxygen concentration and the decreased lifespan of the mutant fly.