Transcription Factor EB Controls Metabolic Flexibility during Exercise.

TitleTranscription Factor EB Controls Metabolic Flexibility during Exercise.
Publication TypeJournal Article
Year of Publication2017
AuthorsMansueto, G, Armani, A, Viscomi, C, D'Orsi, L, De Cegli, R, Polishchuk, EV, Lamperti, C, Di Meo, I, Romanello, V, Marchet, S, Saha, PK, Zong, H, Blaauw, B, Solagna, F, Tezze, C, Grumati, P, Bonaldo, P, Pessin, JE, Zeviani, M, Sandri, M, Ballabio, A
JournalCell Metab
Date Published2017 Jan 10

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.

Alternate JournalCell Metab.
Citation Key10.1016/j.cmet.2016.11.003
PubMed ID28011087
PubMed Central IDPMC5241227
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom
R01 DK110063 / DK / NIDDK NIH HHS / United States