The Endoplasmic Reticulum-associated Degradation System Regulates Mitochondrial Energy Metabolism Activity via Ca2+in Hepatocytes
10.13865/j.cnki.cjbmb.2024.10.1138
- VernacularTitle:内质网相关降解系统通过Ca2+调控肝细胞线粒体能量代谢活性
- Author:
Bei-Er JIANG
1
;
Feng ZHANG
;
Yong-Feng BAI
;
Qi WU
;
Ya-Bing HU
Author Information
1. 温州医科大学附属衢州医院呼吸与危重症医学科,浙江 衢州324000
- Publication Type:Journal Article
- Keywords:
hepatocyte;
organelle interactions;
endoplasmic reticulum associated degradation (ERAD);
mitochondrial function;
calcium ion (Ca2+)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(12):1723-1731
- CountryChina
- Language:Chinese
-
Abstract:
In hepatocytes,the endoplasmic reticulum and mitochondria work together in a reciprocal manner to regulate the physiological functions of the cells.Nevertheless,its precise mechanism remains unknown.Endoplasmic reticulum-associated degradation (ERAD) is a key process for maintaining pro-tein quality in the endoplasmic reticulum.Recent studies have found that ERAD can regulate the adipo-cyte mitochondrial function through mitochondria associated membranes (MAMs).However,it is still unknown how exactly ERAD and mitochondria interact with one another in hepatocytes.In this study,chemical induction and gene deletion were used to induce ERAD deficiency in HepG2 cells.To investi-gate the effect of ERAD on mitochondrial function in hepatocytes,we employed fluorescent labelling,flow analysis,immunoblotting and other methods.The results demonstrated that ERAD dysfunction resulted in a reduction in the mitochondrial membrane potential and ATP levels in HepG2 cells (P<0.01) .Fur-thermore,ERAD dysfunction also disrupted the endoplasmic reticulum and mitochondrial Ca2+homeosta-sis in HepG2 cells,and improved mitochondrial energy metabolism function when endoplasmic reticulum Ca2+release was reduced (P<0.05) .These findings were further validated in ERAD dysfunctional pri-mary hepatocytes,which had been induced by pharmacological agents.The data above indicate that ERAD plays a key regulatory role in endoplasmic reticulum-mitochondrial interactions in hepatocytes.En-hanced ERAD function may boost mitochondrial activity in hepatocytes.This study offers fresh perspec-tives on disorders linked to mitochondrial malfunction.
