PINK1/Parkin介导的线粒体自噬及其在肝脏疾病发生发展中的作用机制

张浩; 张悦; 赵文武; 张敬各

doi:10.3969/j.issn.1001-5256.2020.07.048

PINK1/Parkin介导的线粒体自噬及其在肝脏疾病发生发展中的作用机制

DOI: 10.3969/j.issn.1001-5256.2020.07.048

1. 河北医科大学第二临床医学院
2. 河北医科大学病理生理学教研室

详细信息

中图分类号: R575
计量
- 文章访问数: 1070
- HTML全文浏览量: 63
- PDF下载量: 155
- 被引次数: 0
出版历程
- 出版日期: 2020-07-20

PINK1/Parkin-mediated mitophagy and its mechanism of action in the development and progression of liver diseases

1. The Second Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050017, China; 2. Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China

摘要

摘要:
线粒体自噬是指细胞通过自噬的机制选择性地清除受损线粒体的过程。线粒体自噬的调控机制有几种,但PINK1/Parkin途径被认为是线粒体自噬的主要途径,这一自噬机制在帕金森等多种疾病的发病中有重要作用。介绍了PINK1/Parkin介导的线粒体自噬机制及其在肝脏相关疾病(如非酒精性脂肪性肝病、肝纤维化、肝细胞癌等)中的作用,以期为疾病的治疗提供新的线索和思路。
- 自噬 /
- PINK1/Parkin通路 /
- 非酒精性脂肪性肝病 /
- 肝硬化 /
- 癌,肝细胞
Abstract:
Mitophagy is the process of selective clearance of damaged mitochondria by autophagy. There are several regulatory mechanisms for mitophagy,and the PINK1/Parkin pathway is considered the main pathway for mitophagy. Recent studies have shown that PINK1/Parkin-mediated mitophagy plays an important role in the pathogenesis of various diseases including Parkinson's disease. This article introduces the mechanism of PINK1/Parkin-mediated mitophagy and its role in various liver diseases including nonalcoholic fatty liver disease,liver fibrosis,and hepatocellular carcinoma,in order to provide new clues and ideas for the treatment of diseases.
- autophagy /
- PINK1/Parkin pathway /
- non-alcoholic fatty liver disease /
- liver cirrhosis /
- carcinoma,hepatocellular

HTML全文

参考文献(30)

[1]WHITWORTH AJ,PALLANCK LJ.PINK1/Parkin mitophagy and neurodegeneration-what do we really know in vivo?[J].Curr Opin Genet Dev,2017,44:47-53．

[2]JIA L,LIU Z,SUN L,et al.Acrolein,a toxicant in cigarette smoke,causes oxidative damage and mitochondrial dysfunction in RPE cells:Protection by(R)-alpha-lipoic acid[J].Invest Ophthalmol Vis Sci,2007,48(1):339-348．

[3]MATSUDA N,SATO S,SHIBA K,et al.PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy[J].J Cell Biol,2010,189(2):211-221．

[4]HARPER JW,ORDUREAU A,HEO JM.Building and decoding ubiquitin chains for mitophagy[J].Nat Rev Mol Cell Biol,2018,19(2):93-108．

[5]GKIKAS I,PALIKARAS K,TAVERNARAKIS N.The role of mitophagy in innate immunity[J].Front Immunol,2018,9:1283．

[6]DOVE KK,KLEVIT RE.RING-between-ring E3 ligases:Emerging themes amid the variations[J].J Mol Biol,2017,429(22):3363-3375．

[7]MOSKAL N,RICCIO V,BASHKUROV M,et al.ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway[J].Nat Commun,2020,11(1):88．

[8]ZHOU T,CHANG L,LUO Y,et al.Mst1 inhibition attenuates non-alcoholic fatty liver disease via reversing Parkin-related mitophagy[J].Redox biology,2019,21:101120．

[9]CSAK T,GANZ M,PESPISA J,et al.Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells[J].Hepatology,2011,54(1):133-144．

[10]ZHOU H,DU W,LI Y,et al.Effects of melatonin on fatty liver disease:The role of NR4A1/DNA-PKcs/p53 pathway,mitochondrial fission,and mitophagy[J].J Pineal Res,2018,64(1)．

[11]MA X,LUO Q,ZHU H,et al.Aldehyde dehydrogenase 2 activation ameliorates CCl4-induced chronic liver fibrosis in mice by up-regulating Nrf2/HO-1 antioxidant pathway[J].Cell Mol Med,2018,22:3965-3978．

[12]ZHANG X,LIN C,SONG J,et al.Parkin facilitates proteasome inhibitor-induced apoptosis via suppression of NF-κB activity in hepatocellular carcinoma[J].Cell Death Dis,2019,10(10):719．

[13]XU L,LIN DC,YIN D,et al.An emerging role of PARK2 in cancer[J].J Mol Med(Berl),2014,92(1):31-42．

[14]LI R,XIN T,LI D,et al.Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease:The role of the ERK-CREB pathway and Bnip3-mediated mitophagy[J].Redox Biol,2018,18:229-243．

[15]ZHOU R,YAZDI AS,MENU P,et al.A role for mitochondria in NLRP3inflammasome activation[J].Nature,2011,469(7329):221-225．

[16]SHAO N,YU XY,MA XF,et al.Exenatide delays the progression of nonalcoholic fatty liver disease in C57BL/6 mice,which may involve inhibition of the nlrp3 inflammasome through the mitophagy pathway[J].Gastroenterol Res Pract,2018,2018:1864307．

[17]LIU P,LIN H,XU Y,et al.Frataxin-mediated PINK1-parkindependent mitophagy in hepatic steatosis:The protective effects of quercetin[J].Mol Nutr Food Res,2018,62(16):e1800164．

[18]CHEN L,LANG AL,POFF GD,et al.Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis:Protection by the ALDH2 activator Alda-1[J].Redox Biol,2019,24:101205．

[19]HYUN J,WANG S,KIM J,et al.MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression[J].Nat Commun,2016,7:10993．

[20]KANG JW,HONG JM,LEE SM.Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis[J].J Pineal Res,2016,60(4):383-393．

[21]QIU YN,WANG GH,ZHOU F,et al.PM2.5 induces liver fibrosis via triggering ROS-mediated mitophagy[J].Ecotoxicol Environ Saf,2019,167:178-187．

[22]DING Q,XIE XL,WANG MM,et al.The role of the apoptosis-related protein BCL-B in the regulation of mitophagy in hepatic stellate cells during the regression of liver fibrosis[J].Exp Mol Med,2019,51(1):1-13．

[23]BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countris[J].CA Cancer J Clin,2018,68(6):394-424．

[24]FUJIWARA M,MANRUSAWA H,WANG HQ,et al.Parkin as a tumor suppressor gene for hepatocellular carcinoma[J].Oncogene,2008,27(46):6002-6011．

[25]VOUSDEN KH,PRIVES C.Blinded by the light:The growing complexity of p53[J].Cell,2009,137(3):413-431．

[26]RUDALSKA R,DAUCH D,LONGERICH T,et al.In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer[J].Nat Med,2014,20(10):1138-1146．

[27]ZHENG JF,HE S,ZENG Z,et al.PMPCB silencing sensitizes HCCtumor cells to sorafenib therapy[J].Mol Ther,2019,27(10):1784-1795．

[28]ATTAR EC,AMREIN PC,FRASER JW,et al.Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes(MDS)and acute myeloid leukemia(AML)[J].Leuk Res,2013,37(9):1016-1020．

[29]WEI R,CAO J,YAO S.Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and PINK1/Parkin pathways[J].Cell Stress Chaperones,2018,23(6):1295-1309．

[30]KANG X,WANG H,LI Y,et al.Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human Hep G2 cells[J].Artif Cells Nanomed Biotechnol,2019,47(1):1961-1970.

施引文献

资源附件(0)

访问统计