TY  - JOUR
A1  - Görigk, Sarah
A1  - Ouwens, D. Margriet
A1  - Kuhn, Tanja
A1  - Altenhofen, Delsi
A1  - Binsch, Christian
A1  - Damen, Mareike
A1  - Khuong, Jenny Minh-An
A1  - Kaiser, Katharina
A1  - Knebel, Birgit
A1  - Vogel, Heike
A1  - Schürmann, Annette
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
T1  - Nudix hydrolase NUDT19 regulates mitochondrial function and ATP production in murine hepatocytes
JF  - Biochimica et biophysica acta : Molecular and cell biology of lipids
N2  - Changes in intracellular CoA levels are known to contribute to the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D) in human and rodents. However, the underlying genetic basis is still poorly understood. 
Due to their diverse susceptibility towards metabolic diseases, mouse inbred strains have been proven to serve as powerful tools for the identification of novel genetic factors that underlie the patho-physiology of NAFLD and diabetes. Transcriptome analysis of mouse liver samples revealed the nucleoside diphosphate linked moiety X-type motif Nudt19 as novel candidate gene responsible for NAFLD and T2D development. Knockdown (KD) of Nudt19 increased mitochondrial and glycolytic ATP production rates in Hepa 1-6 cells by 41% and 10%, respectively. 
The enforced utilization of glutamine or fatty acids as energy substrate reduced uncoupled respiration by 41% and 47%, respectively, in non-target (NT) siRNA transfected cells. 
This reduction was prevented upon Nudt19 KD. Furthermore, incubation with palmitate or oleate respectively increased mitochondrial ATP production by 31% and 20%, and uncoupled respiration by 23% and 30% in Nudt19 KD cells, but not in NT cells. 
The enhanced fatty acid oxidation in Nudt19 KD cells was accompanied by a 1.3-fold increased abundance of Pdk4. 
This study is the first to describe Nudt19 as regulator of hepatic lipid metabolism and potential mediator of NAFLD and T2D development.
KW  - Nudt19
KW  - lipid metabolism
KW  - mitochondrial function
KW  - liver metabolism
Y1  - 2022
U6  - https://doi.org/10.1016/j.bbalip.2022.159153
SN  - 1388-1981
SN  - 1879-2618
VL  - 1867
IS  - 6
PB  - Elsevier
CY  - Amsterdam
ER  -