Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?

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Transcription factor EB and TFE3 : new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle? / Markby, Greg Robert; Sakamoto, Kei.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 319, No. 4, 2020, p. E763-E768.

Research output: Contribution to journalReviewResearchpeer-review

Harvard

Markby, GR & Sakamoto, K 2020, 'Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?', American Journal of Physiology: Endocrinology and Metabolism, vol. 319, no. 4, pp. E763-E768. https://doi.org/10.1152/ajpendo.00339.2020

APA

Markby, G. R., & Sakamoto, K. (2020). Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle? American Journal of Physiology: Endocrinology and Metabolism, 319(4), E763-E768. https://doi.org/10.1152/ajpendo.00339.2020

Vancouver

Markby GR, Sakamoto K. Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle? American Journal of Physiology: Endocrinology and Metabolism. 2020;319(4):E763-E768. https://doi.org/10.1152/ajpendo.00339.2020

Author

Markby, Greg Robert ; Sakamoto, Kei. / Transcription factor EB and TFE3 : new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?. In: American Journal of Physiology: Endocrinology and Metabolism. 2020 ; Vol. 319, No. 4. pp. E763-E768.

Bibtex

@article{4fb85da75e614577ad49b7db3b5d2284,
title = "Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?",
abstract = "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 AMPK-peroxisome proliferator-activated receptor γ coactivator 1a (PGC1a) pathway has long been known to orchestrate contraction-mediated adaptive responses, although AMPK- and 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 posttranslational modifications (i.e., phosphorylation) and spatial organization. Under nutrient and energy stress, TFEB and TFE3 are 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 and contractile activity in skeletal muscle.",
keywords = "AMPK, Calcineurin, MTOR, PGC1a, Transcription factor EB",
author = "Markby, {Greg Robert} and Kei Sakamoto",
year = "2020",
doi = "10.1152/ajpendo.00339.2020",
language = "English",
volume = "319",
pages = "E763--E768",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4",

}

RIS

TY - JOUR

T1 - Transcription factor EB and TFE3

T2 - new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle?

AU - Markby, Greg Robert

AU - Sakamoto, Kei

PY - 2020

Y1 - 2020

N2 - 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 AMPK-peroxisome proliferator-activated receptor γ coactivator 1a (PGC1a) pathway has long been known to orchestrate contraction-mediated adaptive responses, although AMPK- and 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 posttranslational modifications (i.e., phosphorylation) and spatial organization. Under nutrient and energy stress, TFEB and TFE3 are 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 and contractile activity in skeletal muscle.

AB - 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 AMPK-peroxisome proliferator-activated receptor γ coactivator 1a (PGC1a) pathway has long been known to orchestrate contraction-mediated adaptive responses, although AMPK- and 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 posttranslational modifications (i.e., phosphorylation) and spatial organization. Under nutrient and energy stress, TFEB and TFE3 are 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 and contractile activity in skeletal muscle.

KW - AMPK

KW - Calcineurin

KW - MTOR

KW - PGC1a

KW - Transcription factor EB

U2 - 10.1152/ajpendo.00339.2020

DO - 10.1152/ajpendo.00339.2020

M3 - Review

C2 - 32830550

AN - SCOPUS:85092332277

VL - 319

SP - E763-E768

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 4

ER -

ID: 251694724