TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

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 () and Jeong-Ho Hong ()
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Jun-Ha Hwang: Korea University
Kyung Min Kim: Korea University
Ho Taek Oh: Korea University
Gi Don Yoo: Korea University
Mi Gyeong Jeong: Ewha Womans University
Hyun Lee: Korea University
Joori Park: Korea University
Kwon Jeong: Korea University
Yoon Ki Kim: Korea University
Young-Gyu Ko: Korea University
Eun Sook Hwang: Ewha Womans University
Jeong-Ho Hong: Korea University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28247-2

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