TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A

This study demonstrates that transcriptional coactivator with PDZ-binding motif (TAZ) stimulates mitochondrial biogenesis in skeletal muscle. Muscle-specific TAZ-knockout (mKO) mice showed decreased mitochondrial biogenesis, respiratory metabolism, and exercise ability compared to wild-type mice. Mechanistically, TAZ stimulates mitochondrial transcription factor A (TFAM) translation via the Rheb/Rhebl1-mTOR axis, stimulating Rhebl1 expression through the TEAD family transcription factor. AAV-mediated Rhebl1 introduction or mTOR activation recovered mitochondrial biogenesis in mKO muscle. mKO mice did not exhibit exercise-induced mitochondrial biogenesis. TAZ is a novel stimulator of mitochondrial biogenesis and exercise-induced muscle adaptation.

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