deoxyguanosine-triphosphate and MELAS-Syndrome

Mitochondrial DNA is subject to increased rates of mutations due to its proximity to the source of reactive oxygen species. Here we show that increased MHC class I (MHC I) expression serves to alert the immune system to cells with mitochondrial mutations. MHC I is overexpressed in fibroblasts with mitochondrial dysfunction from patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and in lymphocytes from purine nucleoside phosphorylase-deficient immune-deficient mice with mitochondrial DNA deletions. Consistent with a role of MHC I in the elimination of cells containing mitochondrial DNA mutations, mice deficient in MHC I accumulate mitochondrial DNA deletions in various tissues. These observations in both mice and humans suggest a role for the immune system in preventing reversion of mitochondrial DNA back into a parasitic state following deleterious mutations affecting mitochondrial oxidative phosphorylation.

Topics: Animals; Deoxyguanine Nucleotides; DNA Damage; DNA-Binding Proteins; DNA, Mitochondrial; Fibroblasts; Histocompatibility Antigens Class I; Humans; Immunologic Deficiency Syndromes; Immunologic Surveillance; Interferon-gamma; MELAS Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteosarcoma; Phosphorylation; Purine-Nucleoside Phosphorylase; Reactive Oxygen Species; STAT1 Transcription Factor; Trans-Activators; Tumor Cells, Cultured