Indigestible mitochondria cause heartburn

Cell Res. 2012 Nov;22(11):1518-20. doi: 10.1038/cr.2012.96. Epub 2012 Jun 19.

Abstract

The link between impaired autophagic flux (autophagus interruptus), damaged mitochondria, and myocardial inflammation has been further tightened with the recent paper by Oka and colleagues, in which failure to degrade mitochondrial DNA exacerbated myocardial inflammation in the context of pressure overload. Using mice with cardiac-specific deletion of the lysosomal DNase II that were subjected to aortic banding, Otsu's group showed that mitochondrial DNA accumulated in lysosomes and resulted in TLR9-dependent production of inflammatory cytokines.

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Antigens, Ly / biosynthesis
  • Autophagy*
  • Cytokines / biosynthesis
  • DNA, Mitochondrial / metabolism*
  • Endodeoxyribonucleases / genetics
  • Gene Deletion
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lysosomes / genetics
  • Lysosomes / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria / genetics*
  • Mitochondria / immunology
  • Mitochondria / metabolism*
  • Myocarditis / genetics
  • Myocarditis / metabolism*
  • Myocardium / immunology*
  • Myocytes, Cardiac / metabolism
  • Receptors, Pattern Recognition / metabolism
  • Toll-Like Receptor 9 / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, Ly
  • CD68 protein, mouse
  • Cytokines
  • DNA, Mitochondrial
  • Interleukin-1beta
  • Interleukin-6
  • Ly6G antigen, mouse
  • Receptors, Pattern Recognition
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • Endodeoxyribonucleases
  • deoxyribonuclease II