Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects
Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects
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DOI：
10.1113/jphysiol.2012.230185
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发表时间：
2012-07-01
影响因子：
5.5
通讯作者：
Hey-Mogensen, Martin
中科院分区：
文献类型：
--
作者：
Larsen, Steen;Nielsen, Joachim;Hey-Mogensen, Martin
骨骼肌线粒体含量在人类受试者之间变化很大。线粒体蛋白质、酶活性和脂质的生化测量通常用作线粒体含量和肌肉氧化能力（OXPHOS）的标志物。本研究的目的是确定这些常用的生化指标与肌肉线粒体含量和OXPHOS的关系有多密切。本研究招募了16名年轻健康男性受试者。受试者完成分级运动试验，以确定最大摄氧量（（V）过点（O2峰值）），并从股外侧肌获得肌肉活检。使用透射电子显微镜成像和OXPHOS测定线粒体含量作为透化纤维中的最大耦合呼吸。感兴趣的生物标志物是柠檬酸合酶（CS）活性，心磷脂含量，线粒体DNA含量（mtDNA），复合物IV蛋白质含量和复合物IIV活性。应用斯皮尔曼相关系数检验和Lin一致性检验来评估标记物与线粒体含量或OXPHOS之间的绝对和相对关联。受试者的（V）过点（O2峰值）（范围为29.9-71.6 ml min（-1）kg（-1））和线粒体含量（细胞体积的4-15%）范围较大。心磷脂含量表现出最强的关联与线粒体含量其次是CS和复合物I的活动。线粒体DNA含量与线粒体DNA含量无关。复合物IV活性表现出最强的协会与肌肉氧化能力，其次是复合物II活性。我们的结论是，心磷脂含量，CS和复合物I活动的生物标志物，表现出最强的关联与线粒体含量，而复合物IV活动与OXPHOS能力在人骨骼肌。
Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how closely associated these commonly used biochemical measures are to muscle mitochondrial content and OXPHOS. Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake ((V)over-dot(O2peak)) and muscle biopsies were obtained from the vastus lateralis. Mitochondrial content was determined using transmission electron microscopy imaging and OXPHOS was determined as the maximal coupled respiration in permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex IV protein content, and complex IIV activity. Spearman correlation coefficient tests and Lin's concordance tests were applied to assess the absolute and relative association between the markers and mitochondrial content or OXPHOS. Subjects had a large range of (V)over-dot(O2peak) (range 29.9-71.6 ml min(-1) kg(-1)) and mitochondrial content (4-15% of cell volume). Cardiolipin content showed the strongest association with mitochondrial content followed by CS and complex I activities. mtDNA was not related to mitochondrial content. Complex IV activity showed the strongest association with muscle oxidative capacity followed by complex II activity. We conclude that cardiolipin content, and CS and complex I activities are the biomarkers that exhibit the strongest association with mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle.