有氧运动对线粒体质子跨膜转运及核糖核苷二磷酸还原酶的影响

本实验通过对有氧运动训练 (无负重游泳 6 0分钟 /天 ,7天 )大鼠游泳运动后的骨骼肌、心肌线粒体质子跨膜转运能力及核糖核苷二磷酸还原酶活性的测定 ,发现有氧运动训练的大鼠在定量运动负荷后 (6 0分钟无负重游泳 ) ,骨骼肌线粒体的质子跨膜转运能力显著提高 (P <0 0 5 ) ,以及线粒体的核糖核苷二磷酸还原酶活性明显高于对照组 (未经训练之大鼠 ,P <0 0 0 1)。而心肌线粒体的以上两项指标变化不甚明显。结果显示 ,骨骼肌线粒体对有氧运动训练的适应过程与其质子跨膜转运能力的提高及核糖核苷二磷酸还原酶活性增加有关。提示骨骼肌线粒体在慢性高氧化磷酸化状态刺激下 ,可能同时导致DNA生物合成的增加 ,即线粒体基因组对其功能变化产生应答反应。心肌线粒体的运动适应过程与骨骼肌线粒体不尽相同。     

运动促进慢性心衰大鼠心肌线粒体生物合成与心肌重构

目的:观察心衰及心衰后进行有氧运动对大鼠心肌线粒体生物力能学、线粒体生物合成以及心功能的影响,探讨心衰的运动康复过程中的心肌线粒体适应机制。方法:雄性Wistar大鼠,心梗组(16只)开胸后结扎左冠状动脉前降支,造成心梗模型,假手术组(16只)开胸但不结扎冠状动脉,其余处理与心梗组相同。术后4周,心梗组和假手术组再随机分为心梗安静组(MI)、心梗运动组(MI+E)和假手术安静组(Sham)、假手术运动组(Sham+E),每组8只。运动组进行跑台训练,运动强度14米/分钟,每天40分钟,每周训练5天,共训练8周。术后12周,超声心动图检查各组大鼠心率(HR),心室收缩末期内径(LVIDs),舒张末期内径(LVIDd)和心功能指标射血分数(EF),缩短分数(FS),每搏输出量(SV),心输出量(CO)。提取心肌线粒体测定态3、态4呼吸和呼吸控制比(RCR),ATP生成活力。Western blot检查心肌线粒体生物合成调控因子PGC-1α,线粒体蛋白COXⅣ、COXⅠ蛋白表达。透射电镜观察各组心肌线粒体形态数量。结果:术后12周,假手术运动组LVIDs、LVIDd、EF、FS、SV、CO与假手术安静组比较无明显变化,态3呼吸、RCR、ATP生成活力高于假手术安静组,PGC-1α、COXⅣ、COXⅠ蛋白表达无明显变化。心梗安静组与假手术安静组比较,LVIDs、LVIDd增加,EF、FS、CO降低,SV无明显差异,态4呼吸增加,RCR、ATP生成活力降低,PGC-1α、COXⅣ、COXⅠ蛋白表达增加。心梗运动组与心梗安静组比较LVIDs、LVIDd增加,EF、FS降低,CO增加,HR增加,SV无明显差异,态3呼吸、RCR、ATP生成活力增加,PGC-1α、COX IV、COX I蛋白表达增加。结论:(1)心衰后心肌线粒体生物合成增加,可能是对心衰后心肌线粒体功能下降的一种代偿性反应。(2)心衰后进行运动训练能促进心肌线粒体生物合成,但线粒体生物合成增加并不能代偿心衰后心功能的下降,并有可能加重心肌重构。     

支链氨基酸对运动大鼠骨骼肌线粒体功能的影响

为探讨支链氨基酸(BCAA)对提高大鼠运动能力的作用,本实验取雄性wistar大鼠21只,随机分为正常组、游泳对照组和游泳补充5%支链氨基酸饲料组.两个游泳组每天游泳训练l小时.10天后,游泳6小时,测定血和骨骼肌乳酸水平,测定骨骼肌糖原含量、骨骼肌线粒体脂质过氧化物(LP0)水平和线粒体膜的流动性以及线粒体矿物元素钙(Ca)、镁(Mg)、钾(K)含量.结果显示BCAA可抑制游泳运动后大鼠的血和骨骼肌乳酸的升高幅度,减少骨骼肌糖原的降低幅度与骨骼肌线粒体LP0的升高幅度,抑制骨骼肌线粒体膜流动性和矿物质元素Ca、Mg、K含量的下降.以上结果表明,BCAA可改善运动后骨骼肌线粒体功能,对抗运动性疲劳.可能有利于提高大鼠的运动能力.     

丁胱亚磺酰亚胺排空组织谷胱甘肽对大鼠心肌谷胱甘肽系统的影响

目的:观察采用谷氨酰半胱氨酸合成酶抑制剂--丁胱亚磺酰亚胺(BSO)排空大鼠心肌谷胱甘肽(GSH)是否影响大鼠心肌组织GSH的稳态,以及是否对GSH代谢相关酶活性及mRNA表达产生影响.方法:采用长时间力竭运动、注射BSO排空GSH两种实验模型,比较对照组与注射BSO组SD大鼠心肌在静息状态和长时间力竭运动后GSH状态及其代谢变化.结果:注射BSO 8天后,大鼠心脏GSH含量分别为对照组?%,且GSH的下降伴随着氧化型谷胱甘肽(GSSG)的下降,GSH/GSSG的比值无显著变化.GSH排空导致GSH代谢酶活性发生适应性变化,注射BSO后心肌中谷胱甘肽过氧化物酶(GPX)活性与对照组相比显著下降(P < 0.001).注射BSO组与对照组相比,心肌谷氨酰转肽酶(GGT)活性显著增加(P < 0.05).注射BSO力竭组与注射BSO组相比,心肌GGT活性显著增加(P < 0.001),心肌注射BSO抑制γ-谷氨酰半胱酸合成酶(GCS)活性,注射BSO力竭组大鼠心肌GCS mRNA表达量高于注射BSO组,表明极度排空谷胱甘肽后,GCS mRNA表达量的增加可能是机体产生的应激反应.     

PGC-1α在运动诱导骨骼肌线粒体生物合成中的调控作用

<正>骨骼肌组织具有高度的可塑性,耐力运动与训练可以诱导提高骨骼肌细胞的呼吸能力以及抗疲劳能力,这种适应性改变包括线粒体蛋白质和自身组分(各种代谢酶以及线粒体DNA)的增加,其结果导致骨骼肌线粒体的数量和质量的增加,这种现象被称为线粒体生物合成[1]。     

衰老和有氧运动对大鼠肝脏线粒体DNA突变的影响

当前研究表明机体衰老与线粒体功能下降关系密切.其中线粒体DNA突变可能是线粒体功能下降与活性氧产生增多的关键因素之一.本研究检测到22月龄大鼠肝脏线粒体DNA出现4834bp缺失,3个月的游泳训练明显降低同龄大鼠线粒体DNA 4834bp缺失发生率.研究同时发现老年大鼠肝脏线粒体复合体I和IV活性明显低于年轻大鼠,而有氧运动可显著升高老年运动大鼠线粒体酶活性.结果表明有氧运动能够减少线粒体DNA突变发生,进而改善线粒体功能,这可能是有氧运动提高线粒体功能,延缓衰老的重要机制.     

游泳训练后大鼠骨骼肌细胞自由基代谢、线粒体膜电位变化与细胞凋亡的关系

目的 :研究游泳训练前后大鼠骨骼肌自由基代谢、线粒体膜电位变化与细胞凋亡的关系 ,寻找评定运动性疲劳与恢复的可行性指标。方法 :5 0只雄性SD大鼠 (10 0± 5 )g ,随机分为对照组 (G1)、训练 1天组 (G2 )、训练 6天组 (G3 )、训练 12天组 (G4 )、训练 18天组 (G5)。用流式细胞仪检测肌细胞线粒体膜电位、DNA倍体分析 ,MDA测定采用硫代巴比妥酸比色法 ,SOD测定使用放免法 ,JEM - 12 0 0EX电镜及脱氧核糖核苷酸末端转移酶介导的缺口末端标记技术 (TUNEL)检测细胞凋亡。结果 :游泳训练后各组骨骼肌细胞线粒体膜电位均发生改变 ,G3 组最低。运动后G3 、G5组的DNA出现凋亡峰。TUNEL染色显示 ,游泳训练后大鼠骨骼肌呈棕黄色的凋亡细胞明显增加 ,G3组比例最高。各训练组之间SOD活性变化差异显著 ,G3 、G4 组MDA数量显著升高。电镜观察G3组肌细胞溶酶体增多 ,部分线粒体嵴消失 ,但膜完整 ,形似空泡 ,枯否细胞活跃。G5组肌细胞的超微结构似G3 组 ,细胞完整。结论 :游泳训练可诱发细胞凋亡 ,不同运动负荷对线粒体膜电位、MDA、SOD的影响各异 ,运动引起线粒体膜电位下降的同时可导致细胞凋亡。线粒体膜电位、SOD/MDA比值变化可能是诱导细胞凋亡的关键因素之一     

有氧耐力训练对增龄大鼠骨骼肌线粒体生物合成的影响

目的:观察增龄大鼠骨骼肌线粒体生物合成的变化特点,探讨有氧耐力训练诱导增龄大鼠骨骼肌线粒体生物合成的分子机理。方法:中等强度跑台运动(64%VO2max,5°,15m/min,45min,每周5天)施加于2、12和17月龄雄性大鼠共12周,对照组正常饲养。12周后取大鼠比目鱼肌和股外侧深层肌进行分子生物学指标检测。结果:(1)增龄过程中,PGC-1α和NRF-1 mRNA表达、mtTFA蛋白表达随增龄显著增加,而mtTFA和COXIV mRNA表达、PGC-1α和COXIV蛋白表达随增龄无显著变化。(2)耐力训练后,5MT组PGC-1α mRNA和蛋白表达、15MT组PGC-1α mRNA表达显著高于各自对照组,5MT和15MT组NRF-1 mRNA表达分别显著高于各自对照组,20MT组PGC-1α mRNA和蛋白表达、NRF-1 mRNA表达相对于20MC组无显著变化,各月龄训练组mtTFA mRNA表达、COXIV mRNA和蛋白表达均显著高于各自对照组。结论:(1)增龄过程中PGC-1α、NRF-1、mtTFA和COXIV mRNA和蛋白水平的变化呈现非同步趋势,提示增龄过程中线粒体生物合成受复杂的多条途径调控;(2)耐力训练能够诱导PGC-1α、NRF-1、mtTFA和COXIV表达显著增加,促进骨骼肌线粒体生物合成;(3)耐力训练诱导骨骼肌线粒体生物合成的适应性积累效应随着大鼠年龄递增逐渐递减。     

骨骼肌线粒体运动适应的分子机制

运动训练可对骨骼肌产生深刻影响,长期反复刺激可使骨骼肌发生适应性改变。而骨骼肌线粒体作为骨骼肌的动力来源,为骨骼肌行使正常功能提供保障,其对运动产生的适应性变化表现为:适宜的运动可促进骨骼肌线粒体生物合成,加速受损或老化线粒体的降解,改变线粒体动力学,重构线粒体网络。对骨骼肌线粒体运动适应机制的研究表明,运动可通过调控过氧化物酶体增殖因子激活受体共激活因子-1α(PGC-1α)、有丝分裂原活化蛋白激酶(P38MAPK)、腺苷单磷酸活化蛋白激酶(AMPK)等因子及其相关信号通路促进线粒体生物合成;运动还可通过影响线粒体融合蛋白、分裂蛋白及AMPK的表达,促进线粒体自噬,以清除损伤或老化的线粒体。通过线粒体新生与损伤线粒体降解,可使线粒体功能增强,线粒体网络结构重构,从而满足运动需求。     

耐力训练对大鼠骨骼肌Mfn2蛋白表达及线粒体功能的影响

目的:观察耐力训练对大鼠骨骼肌线粒体Mfn2蛋白表达及线粒体功能的影响,探讨耐力训练提高骨骼肌有氧代谢能力的线粒体机制。方法:20只雄性Wistar大鼠随机分为对照组(CN)和耐力训练组(ET),每组10只。ET组大鼠进行12周游泳耐力训练,CN组不训练正常饲养。12周后取大鼠腓肠肌,差速离心法提取线粒体,测定锰超氧化物歧化酶(MnSOD)活力、丙二醛(MDA)含量、线粒体呼吸功能、Mfn2基因和蛋白表达。结果:ET组大鼠腓肠肌线粒体MnSOD活性显著高于CN组(P<0.01),MDA含量低于CN组(P<0.05),态3呼吸和Mfn2蛋白表达水平显著高于CN组(P<0.05),呼吸控制比和Mfn2基因表达水平显著高于CN组(P<0.01),态4呼吸无明显变化。结论:12周游泳运动显著上调了Mfn2基因及蛋白表达,这可能是耐力训练提高骨骼肌有氧代谢能力的线粒体机制。     

"解偶联蛋白库"参与急性运动中骨骼肌线粒体解偶联蛋白3的迅速表达

目的研究急性运动中和运动后,骨骼肌线粒体活性氧(ROS)生成与解偶联蛋白3(UCP3)表达的相互关系,探讨骨骼肌胞浆中解偶联蛋白库的作用.方法采用修正的SD大鼠三级递增负荷跑台运动模型,分别选取安静态、运动45、90、120、150min和运动后3、6、12、24h为实验观察点(time course),荧光法测定骨骼肌线粒体ROS生成;荧光定量PCR测定UCP3 mRNA;蛋白印迹法测定骨骼肌和线粒体UCP3蛋白表达;免疫荧光分析检测骨骼肌线粒体外是否存在UCP3蛋白.结果(1)急性运动中及运动后UCP3 mRNA含量和线粒体UCP3蛋白水平均呈先上升后下降的变化趋势UCP3 mRNA含量在运动45min时显著高于安静态(P＜0.01),并持续增高到150min时.虽然在运动后明显下降,但仍显著高于安静态(P＜0.05);线粒体UCP3蛋白含量在运动120min和150min时显著高于安静态(P＜0.001),而骨骼肌UCP3蛋白含量各时间点均未见显著性差异(P＞0.05);(2)免疫荧光分析显示,安静态胞浆内存在大量UCP3蛋白,运动120分钟时明显减少;(3)急性运动中及运动后骨骼肌线粒体ROS生成呈先上升后下降的变化趋势运动45min开始显著升高(P＜0.05),并持续升高至运动120min(P＜0.001),150min时有所下降,但仍显著高于安静态(P＜0.01);运动后3、6、12、24hROS生成均高于安静态,12、24h显著高于安静态(P＜0.05).结论骨骼肌细胞胞浆内存在"UCP3蛋白库",可在运动应激条件下快速动员装载入线粒体,发挥运动抗氧化的快速应答效应.     

The effect of high‐intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

High‐intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60–90% of maximal oxygen uptake (VO_2peak)]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT on mitochondrial fat oxidation in skeletal muscle and adipose tissue. Mitochondrial oxidative phosphorylation (OXPHOS) capacity, mitochondrial substrate sensitivity (K_m^app), and mitochondrial content were measured in skeletal muscle and adipose tissue in healthy overweight subjects before and after 6 weeks of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO_2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. K_m^app for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal muscle and adipose tissue. Maximal OXPHOS capacity with complex I‐ and II‐linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO_2peak. Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal muscle, but not in adipose tissue. Furthermore, mitochondrial fat oxidation was not improved in either skeletal muscle or adipose tissue.     

呼吸链温和解偶联:运动中骨骼肌线粒体抗氧化分子调控的早期事件

目的:研究急性运动诱导线粒体活性氧(ROS)生成的过程中,线粒体内解偶联蛋白(UCPs)介导的温和解偶联(milduncoupling)和抗氧化酶这两种抗氧化体系可能的分工与协同关系及其生物学意义。方法:以SD大鼠3级递增负荷跑台运动为实验模型,分别选取安静态、运动45min、90min、120min和150min为实验观察点(timecourse),测定骨骼肌线粒体ROS生成和脂质过氧化水平(MDA)、线粒体Mn-SOD酶活性、Mn-SOD和解偶联蛋白3(UCP-3)mRNA及蛋白表达。结果:运动过程中ROS生成呈先上升后下降的变化趋势,在运动120min达到峰值,其中运动45min、90min、120min和150min时均较安静时呈显著性升高(分别为P<0.05、P<0.001、P<0.001和P<0.01),150min时下降并具有显著性(P<0.001)。线粒体MDA含量总体呈上升趋势,但变化无显著性。运动过程中Mn-SOD酶活性及其mRNA和蛋白表达水平均无显著性变化,而UCP-3mRNA和蛋白表达水平总体呈上升趋势。其中UCP-3mRNA在运动至90min、120min、150min时较安静时均呈显著性升高(分别为P<0.001、P<0.01和P<0.01),其蛋白表达水平相对滞后一个时间段,运动120min、150min时较安静时显著升高(均为P<0.001)。结论:长时间运动过程中,以UCP-3的先行诱导表达对骨骼肌线粒体氧化还原状态进行调节,相对于Mn-SOD的抗氧化作用,UCP-3的诱导表达是运动中抗氧化的“早期事件”。     

不同训练负荷对大鼠骨骼肌超微结构及线粒体功能的影响

 目的 研究不同训练负荷下,大鼠骨骼肌超微结构及线粒体呼吸链酶复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ和总超氧化物歧化酶(total superoxide dismutase, T-SOD)、锰超氧化物歧化酶(manganese superoxide dismutase, Mn-SOD)和铜锌超氧化物歧化酶(copper zincsuperoxide dismutase, CuZn-SOD)的变化。方法 建立SD大鼠跑台训练模型,将24只大鼠随机分为正常对照组、有氧训练组、无氧训练组,每组8只,正常对照组大鼠笼内正常生活,其他两组分别进行有氧和无氧训练4周,有氧训练时采用递增负荷训练,无氧训练时采用高速训练。采用透射电镜观察骨骼肌形态及线粒体变化。用可见分光光度计检测大鼠骨骼肌线粒体呼吸链酶复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ,以及T-SOD、Mn-SOD和CuZn-SOD活性。结果 相比正常对照组,电镜下有氧训练组线粒体数量增多,三联体结构明显。无氧训练组中可见大量发生肿胀的线粒体,电子密度较正常染色体低;明带与暗带界限不清,粗细肌丝排列紊乱。相比正常对照组,有氧训练组大鼠骨骼肌线粒体呼吸链酶复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ,以及T-SOD、Mn-SOD和CuZn-SOD活性均显著上升(P<0.05);无氧训练组线粒体呼吸链酶复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ以及T-SOD和Mn-SOD活性显著下降(P< 0.05),CuZn-SOD活性[(2.68±0.61)×10³ nkat/mgprot]与正常对照组活性值[(3.73±1.24)×10³ nkat/mgprot]相比,差异无统计学意义(P> 0.05)。结论 不同训练负荷可以改变大鼠骨骼肌线粒体功能,导致抗氧化功能发生相应变化,从而对骨骼肌形态产生较大影响。有氧训练可以改善骨骼肌形态结构和线粒体功能,减轻机体疲劳。     

Muscle structure with low- and high-fat diets in well-trained male runners

Endurance capacity, maximal oxygen uptake capacity (VO2max) and quantitative muscle ultrastructural composition was analyzed in 7 well-trained male runners (mean age 37.1 years, mean VO2max 60 ml/min/kg) after a one month period of a low-fat diet (dietary fat intake 18.4% and a similar period of a high-fat diet (dietary fat intake 40.6%). Between these two interventional periods a washout period of one month was interspersed in which the nutritional fat content was approx. 32%; close to the average American Diet. During all three periods protein content of the nutrition was kept nearly constant at 15%. After the high-fat diet time to exhaustion in the endurance test increased significantly by 21% while VO2max remained unchanged. Muscle mitochondrial volume density remained unchanged while the intramyocellular fat content increased by 60%. Due to large interindividual differences in this variable this difference did not become statistically significant. While some 20% of the mitochondria are located in a subsarcolemmal location, only 10% of the lipid stores are associated with these mitochondria. Less than 2% of the mitochondrial outer surface are in contact with lipid droplets whereas 25-35% of the lipid surface is in contact with mitochondria. None of these variables is significantly altered after a high-fat diet. It is concluded that the change in endurance capacity of the subjects cannot be explained based on the structural changes observed in skeletal muscle tissue. This may be related to methodological problems associated with the determination of intramyocellular fat content.     

Trained men display increased basal heat shock protein content of skeletal muscle

PURPOSE: 1) To compare the baseline levels of heat shock and antioxidant protein content in the skeletal muscle of trained and untrained humans and 2) to characterize the exercise-induced stress response of aerobically trained human skeletal muscle to an acute exercise challenge. METHODS: Resting muscle biopsies were obtained from the vastus lateralis muscle of six untrained and six aerobically trained young males. To characterize the stress response of a trained population, the trained subjects also performed a 45-min nondamaging running exercise protocol at an intensity corresponding to 75% of V O2max. Muscle biopsies were obtained from the vastus lateralis muscle at 48 h and 7 d after exercise. RESULTS: Trained subjects displayed significantly higher (P<0.05) resting levels of heat shock protein 60 (HSP60, 25%), alphaB-crystallin (43%), and manganese superoxide (MnSOD, 45%) protein content compared with untrained subjects. Trained subjects also exhibited no significant change (P > 0.05) in resting levels of HSP70 (16%), HSC70 (13%), and total superoxide dismutase (SOD) activity (46%) compared with untrained subjects. Resting HSP27 levels were unaffected by exercise training (P > 0.05). In the trained subjects, exercise failed to induce significant increases (P>0.05)in muscle content of HSP70, HSC70, HSP60, HSP27, alphaB-crystallin, and MnSOD protein content or in the activity of SOD at any time point after exercise. CONCLUSION: This study demonstrates for the first time that trained men display a selective up-regulation of basal heat shock and antioxidant protein content and do not exhibit a stress response to customary running exercise. It is suggested that an increase in these protective systems functions to maintain homeostasis during the stress of exercise by protecting against disruptions to the cytoskeleton/contractile machinery, by maintaining redox balance, and by facilitating mitochondrial biogenesis.     

低氧训练对AMPKα2三种基因状态鼠骨骼肌HIF-1α mRNA表达的影响

目的:探讨低氧耐力训练对AMPKα2基因敲除(KO)、高表达转基因(OE)及野生型(WT)小鼠骨骼肌HIF-1α mRNA表达的影响。方法:WT、KO及OE鼠各30只,分别随机分为常氧对照组、低氧暴露组和低氧训练组。常氧对照组在常氧状态下饲养14天;低氧暴露组在低氧环境(模拟海拔4000米高度,氧浓度约12.3%)下饲养14天;低氧训练组在与低氧暴露组相同的低氧环境下饲养并连续14天进行跑台训练(12 m/min,1 h/day)。14天后断食12 h取材,测定小鼠骨骼肌AMPKα2蛋白和HIF-1α mRNA表达。结果:(1)OE和WT鼠低氧暴露组、低氧训练组骨骼肌AMPKα2蛋白表达与常氧对照组相比均无显著性差异,KO鼠骨骼肌无AMPKα2蛋白表达。(2)OE鼠、KO鼠和WT鼠低氧训练组骨骼肌HIF-1α mRNA表达量与低氧暴露组相比显著增加。(3)低氧训练下,OE鼠骨骼肌HIF-1α mRNA表达量与WT鼠相比有显著性差异。结论:低氧训练中AMPKα2对骨骼肌HIF-1α mRNA表达起重要作用,但并非HIF-1α表达的必要条件。     

Adaptation of skeletal muscle to endurance exercise.

Skeletal muscle adapts to endurance excerise, such as long distance running, with an increase in the capacity for aerobic metabolism. This is reflected in an increased capacity of whole homogenates and of the mitochondrial fraction of muscle to oxidize pyruvate and long chain fatty acids. Underlying this increase in the ability to obtain energy by respiration is an increase in the levels of a number of mitochondrial enzymes. These include the enzymes involved in fatty acid oxidation, the enzymes of the citric acid cycle, the components of the respiratory chain that link the oxidation of succinate and NADH to oxygen, and coupling factor 1. These increases in mitochondrial enzyme activity appear to be due to an increase in enzyme protein as evidenced by a doubling of the concentration of cytochrome c and a 60% increase in the protein content of the mitochondrial fraction skeletal muscle. Electronmicroscopic studies suggest that increases in both the size and number of mitochondria are responsible for the increase in mitochondrial protein. An alteration in mitochondrial composition also occurs, with some mitochondrial enzymes increasing 2-fold, others increasing only 35% to 60%, while others, including mitochondrial alpha-glycerophosphate dehydrogenase, creatine phosphokinase and adenylate kinase do not increase at all. As a result of these and other exercise induced biochemical adaptations skeletal muscle tends to become more like heart muscle in its enzyme pattern.