Indigestible mitochondria cause heartburn.
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.
Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA 92182, USA. robbieg@sciences.sdsu.edu
Roberta A
RA
Gottlieb
Phyllis-Jean
PJ
Linton
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D000950:Antigens, Ly / Q000096:biosynthesis; D001343:Autophagy; D016207:Cytokines / Q000096:biosynthesis; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics; D017353:Gene Deletion; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000950:Antigens, Ly; D016207:Cytokines; D004272:DNA, Mitochondrial; D004706:Endodeoxyribonucleases; D053583:Interleukin-1beta; D015850:Interleukin-6; D051192:Receptors, Pattern Recognition; D051217:Toll-Like Receptor 9; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C480309:Ly6G antigen, mouse; C495370:Tlr9 protein, mouse; C019329:deoxyribonuclease II