VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
| Autor: | Eddy D Zandee van Rilland, Luz P. Blanco, Xihui Xu, Hee Eun Yoon, Varda Shoshan-Barmatz, Kening Wang, Alexandra L. Brown, Jun Zhu, Mariana J. Kaplan, Rajeev Gupta, Sung-Jun Park, Xinghao Wang, Jay H. Chung, Jeffrey I. Cohen, Myung K. Kim, Martijn Kerkhofs, Hyeog Kang, Shutong Yang, Anna Shteinfer-Kuzmine, Jeonghan Kim |
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| Rok vydání: | 2018 |
| Předmět: |
Mitochondrial DNA
Voltage-dependent anion channel Mitochondrion DNA Mitochondrial Mice Protein Domains Animals Humans Lupus Erythematosus Systemic Voltage-Dependent Anion Channels Multidisciplinary Endodeoxyribonucleases biology Chemistry Neutrophil extracellular traps Cell biology Rats Cytosol Disease Models Animal Oxidative Stress Apoptosis Mitochondrial Membranes biology.protein Interferons Protein Multimerization Bacterial outer membrane VDAC1 |
| Zdroj: | Science (New York, N.Y.). 366(6472) |
| ISSN: | 1095-9203 |
| Popis: | VDACs are MOM's ruin Mitochondrial DNA (mtDNA) is normally kept within the mitochondria. It can be released into the cytosol in response to stress and thus encounter cytosolic DNA sensors, triggering type I interferon responses. During apoptosis, mtDNA release is mediated by macropores in the mitochondrial outer membrane (MOM) created by oligomerization of the proteins BAX and BAK. Kim et al. found that during oxidative stress, mtDNA escapes instead through macropores formed by oligomerization of voltage-dependent anion channels (VDACs) (see the Perspective by Crow). In a mouse model of lupus, an inhibitor of VDAC oligomerization diminished mtDNA release and downstream signaling events. This treatment reduced lupus-like symptoms in the model, suggesting a potential therapeutic route for conditions mediated by mtDNA release. Science , this issue p. 1531 ; see also p. 1445 |
| Databáze: | OpenAIRE |
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