The inner mitochondrial membrane protein ANT1 modulates IL-6 expression via the JNK pathway in macrophages

FEBS Lett. 2018 Nov;592(22):3750-3758. doi: 10.1002/1873-3468.13269. Epub 2018 Oct 24.

Abstract

Mitochondria are increasingly associated with inflammation. Here, we focus on the relationship between inflammation and adenine nucleotide translocator type 1 (ANT1), which is localized in the mitochondrial inner membrane. ANT1 plays an important role in oxidative phosphorylation, and mutations in the ANT1 gene are responsible for mitochondrial diseases. Ample studies have demonstrated that ANT1 has a critical role in cardiomyocytes and neurons, but little has been reported on its functions in immune cells. We knocked down ANT1 expression in macrophages and examined inflammatory cytokine expression after lipopolysaccharide stimulation. ANT1 knockdown reduces the expression of IL-6. JNK, upstream of IL-6, is downregulated, but other MAP kinases and the NF-κB signaling remain unchanged. These results suggest that ANT1 modulates IL-6 expression through JNK in macrophages.

Keywords: JNK; ANT1; IL-6; macrophage.

MeSH terms

  • Adenine Nucleotide Translocator 1 / genetics
  • Adenine Nucleotide Translocator 1 / metabolism*
  • Animals
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Membranes / metabolism*
  • RAW 264.7 Cells
  • RNA Interference

Substances

  • Adenine Nucleotide Translocator 1
  • Interleukin-6
  • Lipopolysaccharides