Transcription Factor EB Controls Metabolic Flexibility during Exercise

Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D'Orsi, Rossella De Cegli, Elena V. Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K. Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E. Pessin, Massimo Zeviani, Marco SandriAndrea Ballabio

Research output: Contribution to journalArticlepeer-review

189 Scopus citations


The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.

Original languageEnglish (US)
Pages (from-to)182-196
Number of pages15
JournalCell metabolism
Issue number1
StatePublished - Jan 10 2017


  • PGC1alpha
  • TFEB
  • autophagy
  • diabetes
  • exercise
  • glucose
  • insulin
  • metabolic flexibility
  • mitochondria
  • mitochondrial fusion

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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