P4HB UFMylation regulates mitochondrial function and oxidative stress
P4HB UFMylation regulates mitochondrial function and oxidative stress
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DOI：
10.1016/j.freeradbiomed.2022.06.237
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Fengling Chen
中科院分区：
文献类型：
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作者：
Jing Zhu;Xirui Ma;Yu Jing;Guangya Zhang;Dandan Zhang;Ziming Mao;Xiaowen Ma;Huifang Liu;Fengling Chen
UFMylation is a ubiquitin-like modification which attaches the ubiquitin-fold modifier 1 to target proteins. To date, only a few UFMylation targets have been identified. In the current study, we demonstrated that P4HB is a new target protein for UFMylation and it can be UFMylated at three lysine residues in the form of mono-UFMylation. P4HB has oxidoreductase, chaperone and isomerase effects. It presents in the endoplasmic reticulum, mitochondria and cytosol. Next, we generated a stable HepG2 cell line, the hepatocellular cells, with defective P4HB UFMylation. Our data showed that P4HB UFMylation defect promotes P4HB protein degradation via the ubiquitin-proteasome pathway. Defective P4HB UFMylation causes mitochondrial function damage, oxidative stress, and endoplasmic reticulum stress in HepG2 cells. These effects are more obvious when treating HepG2 cells with palmitic acid, which is frequently used as one of the cell models of non-alcoholic fatty liver disease (NAFLD). Our results identify UFMylation as a key post-translational modification for the maintenance of P4HB stability and biological functions in HepG2 cells, and point to P4HB UFMylation as a potential direction in the study of NAFLD. • P4HB can be UFMylated at at multiple lysine residues. • P4HB UFMylation defect promotes P4HB protein degradation via the ubiquitin-proteasome pathway. • Defective P4HB UFMylation causes mitochondrial function damage and oxidative stress.
