Editors' ChoicePhysiology

New connections: Better blood vessels and muscles with TFEB

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Sci. Signal.  31 Jan 2017:
Vol. 10, Issue 464, eaam8351
DOI: 10.1126/scisignal.aam8351

TFEB suppresses atherosclerosis and improves muscle performance independently of its role in autophagy.

The transcription factor TFEB activates genes that are involved in lysosomal biogenesis. Lysosomes are organelles that are critical for autophagy, a process by which cells degrade cellular constituents and organelles to remove damaged components or reclaim macromolecules. Two papers show that TFEB has potentially tissue-specific roles that are independent of its role in supporting autophagy. In endothelial cells, Lu et al. found that TFEB abundance increased in response to laminar shear stress, a mechanical stimulus that protects against the development of atherosclerosis. TFEB suppressed oxidative stress and inflammation, processes that contribute to the development of atherosclerosis, by reducing the expression of proinflammatory genes and increasing that of antioxidant genes. When fed a high-fat diet, mice that overexpressed TFEB specifically in endothelial cells had smaller atherosclerotic lesions than their control littermates on the same diet. In skeletal muscle, Mansueto et al. discovered that TFEB transcriptionally activated genes involved in mitochondrial biogenesis and glucose uptake and promoted glycogen synthesis, processes that should improve muscle function and endurance. Indeed, exercise performance was enhanced in mice that acutely overexpressed TFEB in skeletal muscle. In contrast, mice with a skeletal muscle–specific deficiency in TFEB could not sustain high-intensity exercise, in part because their muscles quickly depleted glycogen stores. Thus, enhancing TFEB function could reduce the development of atherosclerosis and muscle fatigue.

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