Mito-TEMPO Ameliorates Sodium Palmitate Induced Ferroptosis in MIN6 Cells through PINK1/Parkin-Mediated Mitophagy  

作　　者：Baolei Chang Yanyu Su Tingting Li Yanxia Zheng Ruirui Yang Heng Lu Hao Wang Yusong Ding 

机构地区：[1]College of Public Health,Xinjiang Medical University,Urumqi 830011,Xinjiang,China [2]Department of Preventive Medicine,School of Medicine,Shihezi University,Shihezi 832003,Xinjiang,China [3]Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security,the Xinjiang Production and Construction Corps,Shihezi 832003,Xinjiang,China

出　　处：《Biomedical and Environmental Sciences》2024年第10期1128-1141,共14页生物医学与环境科学（英文版）

基　　金：supported by a grant from the Science and Technology Tackling Programme Project of Xinjiang Production and Construction Corps(2021AB030).

摘　　要：Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreaticβ-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondriatargeted antioxidant(Mito-TEMPO)to protect pancreaticβ-cells from ferroptosis by mitigating lipid peroxidation becomes crucial.Methods MIN6 cells were cultured in vitro with 100μmol/L sodium palmitate(SP)to simulate diabetes.FerroOrange was utilized for the detection of Fe2+fluorescence staining,BODIPY581/591C11 for lipid reactive oxygen species,and MitoSox-Red for mtROS.Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence.Western blotting was employed to quantify protein levels of Acsl4,GPX4,FSP1,FE,PINK1,Parkin,TOMM20,P62,and LC3.Subsequently,interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone(CCCP)to observe changes in ferroptosis and mitophagy within MIN6 cells.Results We found that SP induced a dose-dependent increase in Fe2+and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins.Through bioinformatics analysis,it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes.Additionally,SP decreased the expression of mitophagy-related proteins PINK1 and Parkin,leading to mtROS overproduction.Conversely,Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin,thereby reducing the occurrence of ferroptosis in MIN6 cells.CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells.Conclusion In summary,Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells.Consequently,this decreased iron overload and lipid peroxidation,ultimately safeguarding the cells from ferroptosis.

关 键 词：MtROS Ferroptosis MITOPHAGY MIN6 Bioinformatical analysis Type 2 diabetes 

分 类 号：R318[医药卫生—生物医学工程]