Abstract

17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) plays an important role in mitochondrial fatty acid metabolism and is also involved in mitochondrial tRNA maturation. HSD17B10 missense mutations cause HSD10 mitochondrial disease (HSD10MD). HSD17B10 with mutations identified from cases of HSD10MD show loss of function in dehydrogenase activity and mitochondrial tRNA maturation, resulting in mitochondrial dysfunction. It has also been implicated to play roles in the development of Alzheimer disease (AD) and tumorigenesis. Here, we found that HSD17B10 is a new substrate of NAD-dependent deacetylase Sirtuin 3 (SIRT3). HSD17B10 is acetylated at lysine residues K79, K99 and K105 by the acetyltransferase CBP, and the acetylation is reversed by SIRT3. HSD17B10 acetylation regulates its enzymatic activity and the formation of mitochondrial RNase P. Furthermore, HSD17B10 acetylation regulates the intracellular functions, affecting cell growth and cell resistance in response to stresses. Our results demonstrated that acetylation is an important regulation mechanism for HSD17B10 and may provide insight into interrupting the development of AD.

Details

Title
Deacetylation of HSD17B10 by SIRT3 regulates cell growth and cell resistance under oxidative and starvation stresses
Author
Liu, Lu 1 ; Chen Shuaiyi 1 ; Yu, Miao 1 ; Ge Chenxu 1 ; Ren Mengmeng 1 ; Liu Boya 1 ; Yang, Xin 1 ; Christian, Thomas W, Jr 2 ; Ya-Ming, Hou 2 ; Zou Junhua 1 ; Wei-Guo, Zhu 3 ; Luo Jianyuan 4 

 Peking University Health Science Center, Department of Medical Genetics, Center for Medical Genetics, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
 Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, USA (GRID:grid.265008.9) (ISNI:0000 0001 2166 5843) 
 Shenzhen University School of Medicine, Department of Biochemistry and Molecular Biology, Shenzhen, China (GRID:grid.263488.3) (ISNI:0000 0001 0472 9649) 
 Peking University Health Science Center, Department of Medical Genetics, Center for Medical Genetics, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319); Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
Publication year
2020
Publication date
Jul 2020
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2426354693
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.