TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

• Published in: Nature communications Vol. 13; no. 1; pp. 653 - 12
• Main Authors: Hwang, Jun-Ha, Kim, Kyung Min, Oh, Ho Taek, Yoo, Gi Don, Jeong, Mi Gyeong, Lee, Hyun, Park, Joori, Jeong, Kwon, Kim, Yoon Ki, Ko, Young-Gyu, Hwang, Eun Sook, Hong, Jeong-Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/95; 14; 14/19; 14/34; 38; 38/77; 38/88; 38/89; 631/80/642/333; 631/80/86; 692/698/1671/1668/1973; Adaptation; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adenosine Triphosphate - metabolism; Animals; Biosynthesis; Cell Line; Cells, Cultured; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Energy requirements; Fibroblasts - cytology; Fibroblasts - metabolism; HEK293 Cells; Homology; Humanities and Social Sciences; Humans; Mice; Mice, Knockout; Mitochondria; Mitochondria, Muscle - genetics; Mitochondria, Muscle - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; multidisciplinary; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Myoblasts - cytology; Myoblasts - metabolism; Organelle Biogenesis; Organelles; Physical Conditioning, Animal; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Skeletal muscle; Stimulators; TOR protein; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28247-2

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. Mitochondrial biogenesis is stimulated to meet energy requirements in response to extracellular signals including exercise. TAZ is revealed as a novel stimulator for mitochondrial biogenesis and facilitates exercise-induced muscle adaptation.