Effects of YAP in the Regulation of Mitochondrial Function

LI Jin¹, Du Miaomiao¹, LÜ Jianxin^1,2, YE Ziyang³*

(¹School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000, China; ²Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China; ³Department of Orthopedics, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, China)

Abstract:

YAP (yes-associated protein) is transcriptional co-activator and functions as a downstream effector of Hippo signaling pathway. YAP has been recognized as a transcriptional regulator of multiple metabolic enzymes, however its role in the regulation of mitochondrial function is not known. In this study, inhibition of YAP by either chemical or KD (gene knockdown) in HeLa cells enhanced mitochondrial function by increase the assembly of mitochondrial respiratory chain complexes. Mechanistically, KD of YAP positively regulates the expression of transcriptional factors related to mitochondrial biogenesis including Nrf1, RXRα, and POLG. Whereas HIF1-alpha, a transcriptional factor which negatively associated with mitochondrial function, was inhibited by the KD of YAP in HeLa cells. Moreover, decreased expression of YAP may be responsible for the enhanced mitochondrial function in glucose deprived HeLa cells. Altogether, YAP is a negative regulator of mitochondrial function and its suppression in glucose deprived cells enhances mitochondrial function.

CSTR: 32200.14.cjcb.2020.03.0012