VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease

doi:10.1126/science.aav4011

GSTDTAP

DOI	10.1126/science.aav4011
	VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
	Kim, Jeonghan 1; Gupta, Rajeev 2,3; Blanco, Luz P.4; Yang, Shutong 1; Shteinfer-Kuzmine, Anna 2,3; Wang, Kening 5; Zhu, Jun 6,7; Yoon, Hee Eun 1; Wang, Xinghao 4; Kerkhofs, Martijn 8,9; Kang, Hyeog 1; Brown, Alexandra L.1; Park, Sung-Jun 1; Xu, Xihui 1; van Rilland, Eddy Zandee 1,10; Kim, Myung K.1; Cohen, Jeffrey I.5; Kaplan, Mariana J.4; Shoshan-Barmatz, Varda 2,3; Chung, Jay H.1
	2019-12-20
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2019
卷号	366 期号:6472 页码:1531-+
文章类型	Article
语种	英语
国家	USA; Israel; Belgium
英文摘要	Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type I interferon (IFN) response. Mitochondrial outer membrane permeabilization, which isrequired for mtDNA release, has been extensively studied inapoptotic cells, but little isknown about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues inthe N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000503861000059
WOS关键词	DNA ; ACTIVATION ; CALCIUM ; PREVENT
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/226513
专题	环境与发展全球科技态势
作者单位	1.NHLBI, Lab Obes & Aging Res, Cardiovasc Branch, Bldg 10, Bethesda, MD 20892 USA; 2.Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel; 3.Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, IL-84105 Beer Sheva, Israel; 4.NIAMSD, Syst Autoimmun Branch, Bethesda, MD 20892 USA; 5.NIAID, Med Virol Sect, Infect Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA; 6.NHLBI, Syst Biol Ctr, Bldg 10, Bethesda, MD 20892 USA; 7.Mokobio Biotechnol R&D Ctr, Rockville, MD 20850 USA; 8.Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Mol & Cellular Signaling, B-3000 Leuven, Belgium; 9.Katholieke Univ Leuven, Leuven Kanker Inst, B-3000 Leuven, Belgium; 10.Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA
推荐引用方式 GB/T 7714	Kim, Jeonghan,Gupta, Rajeev,Blanco, Luz P.,et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease[J]. SCIENCE,2019,366(6472):1531-+.
APA	Kim, Jeonghan.,Gupta, Rajeev.,Blanco, Luz P..,Yang, Shutong.,Shteinfer-Kuzmine, Anna.,...&Chung, Jay H..(2019).VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease.SCIENCE,366(6472),1531-+.
MLA	Kim, Jeonghan,et al."VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease".SCIENCE 366.6472(2019):1531-+.