UM
Mono-2-ethylhexyl phthalate drives progression of PINK1-parkin-mediated mitophagy via increasing mitochondrial ROS to exacerbate cytotoxicity
Xu,Jian1,2; Wang,Liming3; Zhang,Lihuan1; Zheng,Fang1; Wang,Fang1; Leng,Jianhang2; Wang,Keyi2; Héroux,Paul4; Shen,Han Ming5; Wu,Yihua1; Xia,Dajing1
2021
Source PublicationRedox Biology
ISSN2213-2317
Volume38
AbstractPhthalate ester plasticizers are used to improve the plasticity and strength of plastics. One of the most widely used and studied, di-2-ethylhexyl phthalate (DEHP), has been labeled as an endocrine disruptor. The major and toxic metabolic derivative of DEHP, mono-2-ethylhexyl phthalate (MEHP), is capable of interfering with mitochondrial function, but its mechanism of action on mitophagy remains elusive. Here, we report that MEHP exacerbates cytotoxicity by amplifying the PINK1-Parkin-mediated mitophagy pathway. First, MEHP exacerbated mitochondrial damage induced by low-dose CCCP via increased reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (MMP), and enhanced fragmentation in mitochondria. Second, co-exposure to MEHP and CCCP (“MEHP-CCCP”) induced robust mitophagy. Mechanistically, MEHP-CCCP stabilized PINK1, increased the level of phosphorylated ubiquitin (pSer 65-Ub), and led to Parkin mitochondrial translocation and activation. Third, MEHP-CCCP synergistically caused more cell death, while inhibition of mitophagy, either through chemical or gene silencing, reduced cell death. Finally and importantly, co-treatment with N-acetyl cysteine (NAC) completely counteracted the effects of MEHP-CCCP, suggesting that mitochondrial ROS played a vital role in this process. Our results link mitophagy and MEHP cytotoxicity, providing an insight into the potential roles of endocrine disrupting chemicals (EDCs) in human diseases such as Parkinson's disease.
KeywordCell death Cytotoxicity MEHP Mitochondrial ROS PINK1-Parkin-mediated mitophagy
DOI10.1016/j.redox.2020.101776
URLView the original
Language英语
Fulltext Access
Citation statistics
Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorWu,Yihua
Affiliation1.Department of Toxicology of School of Public Health,And Department of Gynecologic Oncology of Women's Hospital,Zhejiang University School of Medicine,Hangzhou,310058,China
2.Department of Central Laboratory,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou,310006,China
3.Hunan Key Laboratory of Medical Epigenomics,Department of Dermatology,Second Xiangya Hospital,Central South University,Changsha,China
4.Department of Epidemiology,Biostatistics and Occupational Health,McGill University,Canada
5.Faculty of Health Sciences,University of Macau,Macau SAR,China
Recommended Citation
GB/T 7714
Xu,Jian,Wang,Liming,Zhang,Lihuan,et al. Mono-2-ethylhexyl phthalate drives progression of PINK1-parkin-mediated mitophagy via increasing mitochondrial ROS to exacerbate cytotoxicity[J]. Redox Biology,2021,38.
APA Xu,Jian,Wang,Liming,Zhang,Lihuan,Zheng,Fang,Wang,Fang,Leng,Jianhang,Wang,Keyi,Héroux,Paul,Shen,Han Ming,Wu,Yihua,&Xia,Dajing.(2021).Mono-2-ethylhexyl phthalate drives progression of PINK1-parkin-mediated mitophagy via increasing mitochondrial ROS to exacerbate cytotoxicity.Redox Biology,38.
MLA Xu,Jian,et al."Mono-2-ethylhexyl phthalate drives progression of PINK1-parkin-mediated mitophagy via increasing mitochondrial ROS to exacerbate cytotoxicity".Redox Biology 38(2021).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Xu,Jian]'s Articles
[Wang,Liming]'s Articles
[Zhang,Lihuan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Xu,Jian]'s Articles
[Wang,Liming]'s Articles
[Zhang,Lihuan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Xu,Jian]'s Articles
[Wang,Liming]'s Articles
[Zhang,Lihuan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.