VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease, 2019, Kim et al

Andy · Dec 21, 2019

Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little is known 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 in the 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.
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Paywall, https://science.sciencemag.org/content/366/6472/1531
Sci hub, https://sci-hub.se/10.1126/science.aav4011

Trish · Dec 21, 2019

Mouse model.

Jaybee00 · Dec 27, 2019

https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(18)30573-4

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in b Cells

Haven’t read either, but wonder if oligomerization results from overexpression.

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VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease, 2019, Kim et al

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VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease, 2019, Kim et al

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Trish Moderator Staff Member

Jaybee00 Senior Member (Voting Rights)

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