NDUFA9 and its crotonylation modification promote browning of white adipocytes by activating mitochondrial function in mice

Yuexia Liu; Zunhai Liu; Zeyu Ren; Qiannan Han; Xinhao Chen; Jialu Han; Guiping Qiu; Chao Sun

doi:10.1016/j.biocel.2024.106583

NDUFA9 and its crotonylation modification promote browning of white adipocytes by activating mitochondrial function in mice

Int J Biochem Cell Biol. 2024 Apr 22:171:106583. doi: 10.1016/j.biocel.2024.106583. Online ahead of print.

Authors

Yuexia Liu¹, Zunhai Liu¹, Zeyu Ren¹, Qiannan Han¹, Xinhao Chen¹, Jialu Han¹, Guiping Qiu¹, Chao Sun²

Affiliations

¹ College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
² College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: sunchao2775@163.com.

PMID: 38657899
DOI: 10.1016/j.biocel.2024.106583

Abstract

Protein crotonylation plays a role in regulating cellular metabolism, gene expression, and other biological processes. NDUFA9 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9) is closely associated with the activity and function of mitochondrial respiratory chain complex I. Mitochondrial function and respiratory chain are closely related to browning of white adipocytes, it's speculated that NDUFA9 and its crotonylation are associated with browning of white adipocytes. Firstly, the effect of NDUFA9 on white adipose tissue was verified in white fat browning model mice, and it was found that NDUFA9 promoted mitochondrial respiration, thermogenesis, and browning of white adipose tissue. Secondly, in cellular studies, it was discovered that NDUFA9 facilitated browning of white adipocytes by enhancing mitochondrial function, mitochondrial complex I activity, ATP synthesis, and mitochondrial respiration. Again, the level of NDUFA9 crotonylation was increased by treating cells with vorinostat (SAHA)+sodium crotonate (NaCr) and overexpressing NDUFA9, it was found that NDUFA9 crotonylation promoted browning of white adipocytes. Meanwhile, the acetylation level of NDUFA9 was increased by treating cells with SAHA+sodium acetate (NaAc) and overexpressing NDUFA9, the assay revealed that NDUFA9 acetylation inhibited white adipocytes browning. Finally, combined with the competitive relationship between acetylation and crotonylation, it was also demonstrated that NDUFA9 crotonylation promoted browning of white adipocytes. Above results indicate that NDUFA9 and its crotonylation modification promote mitochondrial function, which in turn promotes browning of white adipocytes. This study establishes a theoretical foundation for the management and intervention of obesity, which is crucial in addressing obesity and related medical conditions in the future.

Keywords: Acetylation modification; Browning of white adipocytes; Crotonylation modification; Mitochondrial; NDUFA9.