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TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

Biology

TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

J. Hwang, K. M. Kim, et al.

This groundbreaking study reveals that TAZ, a transcriptional coactivator, plays a crucial role in stimulating mitochondrial biogenesis in skeletal muscle. Research conducted by Jun-Ha Hwang and colleagues uncovers the mechanisms through which TAZ influences exercise ability and metabolism. The findings highlight the importance of TAZ in muscle adaptation during exercise, paving the way for new interventions in enhancing muscle performance.

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~3 min • Beginner • English
Abstract
Mitochondria are energy-generating organelles and mitochondrial biogenesis is stimulated to meet energy requirements in response to extracellular stimuli, including exercise. However, the mechanisms underlying mitochondrial biogenesis remain unknown. Here, we demonstrate that transcriptional coactivator with PDZ-binding motif (TAZ) stimulates mitochondrial biogenesis in skeletal muscle. In muscle-specific TAZ-knockout (mKO) mice, mitochondrial biogenesis, respiratory metabolism, and exercise ability were decreased compared to wild-type mice. Mechanistically, TAZ stimulates the translation of mitochondrial transcription factor A via Ras homolog enriched in brain (Rheb)/Rheb like 1 (Rhebl1)-mTOR axis. TAZ stimulates Rhebl1 expression via TEA domain family transcription factor. Rhebl1 introduction by adeno-associated virus or mTOR activation recovered mitochondrial biogenesis in mKO muscle. Physiologically, mKO mice did not stimulate exercise-induced mitochondrial biogenesis. Collectively, our results suggested that TAZ is a novel stimulator for mitochondrial biogenesis and exercise-induced muscle adaptation.
Publisher
Nature Communications
Published On
Feb 03, 2022
Authors
Jun-Ha Hwang, Kyung Min Kim, Ho Taek Oh, Gi Don Yoo, Mi Gyeong Jeong, Hyun Lee, Joori Park, Kwon Jeong, Yoon Ki Kim, Young-Gyu Ko, Eun Sook Hwang, Jeong-Ho Hong
Tags
TAZ
mitochondrial biogenesis
skeletal muscle
exercise adaptation
Rheb/mTOR axis
TFAM
Rhebl1
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