运动、线粒体转录因子A与骨骼肌萎缩

Exercise,Mitochondrial Transcription Factor A and Skeletal Muscle Atrophy

疾病、衰老、损伤、营养减少和肌肉废用等多种原因可引起骨骼肌萎缩,并且线粒体功能障碍始终伴随着骨骼肌萎缩的发生和发展。线粒体转录因子A(mitochondrial transcription factor A,TFAM或m TFA)作为调节线粒体功能的重要转录因子,能与线粒体DNA (mitochondrial DNA,mt DNA)结合,从而调节mt DNA的复制、转录以及维护线粒体的正常功能。TFAM与骨骼肌萎缩关系密切。运动是高效、经济、方便和可行的防治骨骼肌萎缩手段。运动通过提高骨骼肌中与线粒体生物合成密切相关的过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferatoractivated receptorγcoactivator-1 alpha,PGC-1α)的活性和保护、运输TFAM的热激蛋白(heat shock proteins,HSPs)表达,以及调节TFAM的表观遗传学状态,如改变microRNAs表达、DNA甲基化和蛋白质的磷酸化、糖基化、泛素化等,促进TFAM的表达和生物学功能。因此,本文就TFAM在骨骼肌萎缩中的作用及运动对其的调控影响进行综述。

Skeletal muscle atrophy is caused by a host of factors including diseases,aging,injury,nutritional decrement and muscle disuse.The mitochondrial dysfunction is associated with the occurrence and development of skeletal muscle atrophy.Mitochondrial transcription factor A(TFAM or m TFA),as an important transcription factor,can interact with mitochondrial DNA(mt DNA),which regulates the replication and transcription of mt DNA and maintains the normal functions of mitochondria.TFAM is closely associated with atrophy of skeletal muscle.Exercise is an efficient,economical,convenient and feasible method to prevent skeletal muscle atrophy.Exercise may promote the expression and biological functions of TFAM in skeletal muscle by improving the expression of peroxisome proliferator activated receptor gamma coactivator-1 alpha(PGC-1α),a well-known activator of the transcription of TFAM and mitochondrial biogenesis,and heat shock proteins(HSPs)which is to protect and transport TFAM.Exercise may also change the epigenetic modifications of TFAM,such as changing the expression of microRNAs,DNA methylation and protein phosphorylation,glycosylation,ubiquitination,and so on.Therefore,this review summarized the role of TFAM in skeletal muscle atrophy and the effects of exercise on its expression.