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; Jeong-Ho Hong

doi:10.1038/s41467-022-28247-2

TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

Nat Commun. 2022 Feb 3;13(1):653. doi: 10.1038/s41467-022-28247-2.

Authors

Affiliations

¹ Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea.
² College of Pharmacy, Ewha Womans University, Seoul, 03760, Korea.
³ College of Pharmacy, Ewha Womans University, Seoul, 03760, Korea. [email protected].
⁴ Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Adenosine Triphosphate / metabolism
Animals
Cell Line
Cells, Cultured
DNA, Mitochondrial / genetics
DNA, Mitochondrial / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism
Fibroblasts / cytology
Fibroblasts / metabolism
HEK293 Cells
Humans
Mice
Mice, Knockout
Mitochondria, Muscle / genetics*
Mitochondria, Muscle / metabolism
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Muscle, Skeletal / cytology
Muscle, Skeletal / metabolism
Myoblasts / cytology
Myoblasts / metabolism
Organelle Biogenesis*
Physical Conditioning, Animal*
Reactive Oxygen Species / metabolism
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

Adaptor Proteins, Signal Transducing
DNA, Mitochondrial
DNA-Binding Proteins
Mitochondrial Proteins
Reactive Oxygen Species
Transcription Factors
Wwtr1 protein, mouse
mitochondrial transcription factor A
Adenosine Triphosphate