当前位置: X-MOL 学术J. Appl. Physiol. Endocrinol. Metab. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Transcription Factor EB (TFEB): new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?
American Journal of Physiology-Endocrinology and Metabolism ( IF 5.1 ) Pub Date : 2020-08-24 , DOI: 10.1152/ajpendo.00339.2020
Greg Robert Markby 1 , Kei Sakamoto 1
Affiliation  

In response to the increased energy demands of contractions, skeletal muscle adapts remarkably well through acutely regulating metabolic pathways to maintain energy balance and in the longer term by regulating metabolic reprogramming such as remodeling and expanding the mitochondrial network. This long-term adaptive response involves modulation of gene expression at least partly through the regulation of specific transcription factors and transcriptional coactivators. The AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor­γ co-activator 1a (PGC1a) pathway has long been known to orchestrate contraction-mediated adaptive responses, although AMPK-/PGC1a-independent pathways have also been proposed. Transcription factor EB (TFEB) and TFE3, known as important regulators of lysosomal biogenesis and autophagic processes, have emerged as new metabolic coordinators. The activity of TFEB/TFE3 is regulated through post-translational modifications (i.e. phosphorylation) and spatial organization. Under nutrient/energy stress, TFEB/TFE3 get dephosphorylated and translocate to the nucleus where they activate transcription of their target genes. It has recently been reported that exercise promotes nuclear translocation and activation of TFEB/TFE3 in mouse skeletal muscle through the Ca2+-stimulated protein phosphatase calcineurin. Skeletal muscle-specific ablation of TFEB exhibits impaired glucose homeostasis and mitochondrial biogenesis with reduced metabolic flexibility during exercise, and global TFE3 depletion results in diminished endurance and abolished exercise-induced metabolic benefits. Transcriptomic analysis of the muscle-specific TFEB-null mice has demonstrated that TFEB regulates the expression of genes involved in glucose metabolism and mitochondrial homeostasis. This review aims to summarize and discuss emerging roles for TFEB/TFE3 in metabolic and adaptive responses to exercise/contractile activity in skeletal muscle.

中文翻译:

转录因子EB(TFEB):新的代谢调节剂介导骨骼肌运动的适应性反应?

响应于增加的收缩能量需求,骨骼肌可以通过急性调节代谢途径来维持能量平衡,并在更长的时间内通过调节代谢重编程(例如重塑和扩展线粒体网络)而显着适应。这种长期的适应性反应至少部分地通过调节特定的转录因子和转录共激活因子来调节基因表达。长期以来,AMP激活的蛋白激酶(AMPK)-过氧化物酶体增殖物激活的受体γ共激活因子1a(PGC1a)途径可以协调收缩介导的适应性反应,尽管还提出了不依赖AMPK // PGC1a的途径。转录因子EB(TFEB)和TFE3,被称为溶酶体生物发生和自噬过程的重要调节剂,已经成为新的代谢协调者。TFEB / TFE3的活性通过翻译后修饰(即磷酸化)和空间组织来调节。在营养/能量胁迫下,TFEB / TFE3被去磷酸化并转移至细胞核,从而激活其靶基因的转录。最近有报道称,运动通过Ca促进小鼠骨骼肌的核易位和TFEB / TFE3的活化。2+刺激的蛋白磷酸酶钙调神经磷酸酶。TFEB的骨骼肌特异性消融表现出受损的葡萄糖稳态和线粒体生物发生,并且在运动过程中代谢弹性降低,而整体TFE3消耗导致耐力下降,运动诱导的代谢益处消失。对肌肉特异性TFEB无效小鼠的转录组学分析表明,TFEB调节参与葡萄糖代谢和线粒体稳态的基因的表达。这篇综述旨在总结和讨论TFEB / TFE3在代谢和对骨骼肌运动/收缩活动的适应性反应中的新兴作用。
更新日期:2020-08-24
down
wechat
bug