[대학원 생명과학과 세미나 안내]
연사 : 김정한 교수(가톨릭 의과대학 생화학 교실)
연제 : Inhibition of mitochondrial DNA release as a therapeutic strategy for inflammatory diseases.
일시 : 2021년 11월 05일 (금) 오후 5시
장소 : 온라인 화상 강의로 진행됩니다.
초청교수 : 고제상 교수
Abstract
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, triggering immunostimulatory pathways such as the type-Ι interferon response. Pores formed in the outer membrane of mitochondria (OMM) can promote mtDNA release; however, the identity of such a pore in living cells is not well characterized. Here, we provide genetic and biochemical evidence demonstrating that the oligomerization of voltage-dependent anion channel 1 (VDAC1) in the OMM promotes mtDNA release and triggers the type-Ι interferon response in living cells. In addition to forming OMM pores, VDAC1 interacts with mtDNA via its positively charged residues in the N-terminal domain and increases both VDAC1 oligomerization and type-Ι interferon response. VBIT-4, which inhibits VDAC1 oligomerization, decreases mtDNA release, type-Ι interferon 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.