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Functions of FoxO Transcription Factors in Skeletal Muscle Homeostasis and Exercise-Related Regulation

ZHANG Qing;DING Shuzhe;Key Laboratory of Adolescent Health Assessment and Exercise Intervention,Ministry of Education,East China Normal University;School of Physical Education and Health Care,East China Normal University;Laboratory of Molecular Biology of the Cell,Ecole Normale Supérieure de Lyon;  
Fox Os are highly conserved transcription factors with significant roles in cellular homeostasis. The four Fox O members are Fox O1,Fox O3,Fox O4,and FOXO6. This reviewdiscusses the central role of these proteins in the control of skeletal muscle homeostasis. Fox O1 and Fox O3 are key factors of muscle energy homeostasis through the control of glycolytic and lipolytic flux,and mitochondrial metabolism. They are important regulators of muscle fiber types and protein breakdown. According to their activation level,Fox O proteins can exhibit different functions. For example,a basal level of Fox O factors is essential for cellular homeostasis and these proteins are required for muscle adaptation to exercise. Different types of exercise have diverse effects on them. However,exacerbated activation may be present in many diseases,resulting in atrophy and metabolic disorders. A better understanding of these transcription factors functions will facilitate the development of newtherapeutic approaches to prevent or limit the muscle wasting that prevails in multiple pathological states,such as immobilization,denervated conditions,neuromuscular disease,aging,diabetes,AIDS,and cancer.
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