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The role of the mitochondrial voltage‐dependent anion channel in obesity and inflammation
Author(s) -
Kim Jeonghan,
Yoon Heeeun,
Chung Jay
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02749
Subject(s) - voltage dependent anion channel , vdac1 , microbiology and biotechnology , mitochondrion , inflammation , cytosol , cardiolipin , chemistry , biology , bacterial outer membrane , immunology , biochemistry , gene , membrane , phospholipid , escherichia coli , enzyme
Stressed mitochondria can release mitochondrial DNA (mtDNA) into the cytosol via the mitochondrial outer membrane (MOM), where it interacts with and activates a large number of immunostimulatory DNA sensors, which can promote inflammation and metabolic disorders. The voltage‐dependent anion channel (VDAC), which in the mammalian mitochondria is represented by three isoforms (VDAC1, VDAC2, and VDAC3), is the most abundant protein in the MOM and regulates metabolism, inflammasome activation, and the type‐I interferon signaling pathway. We found that VDAC‐mediated cytosolic mtDNA release can activate the type‐I interferon signaling pathway and cause obesity and autoimmune diseases such as systemic lupus erythematosus (SLE). The VDAC oligomerization inhibitor VBIT‐4 decreases both adipogenesis and weight gain in leptin‐deficient (ob/ob) mice. Also, in a mouse model of lupus, VBIT‐4 ameliorated lupus‐like symptoms through diminishing mtDNA release and NETosis. Our findings support VDAC oligomerization as a new therapeutic target for obesity and inflammatory disease associated with mtDNA release.