Voltage-Dependent Anion Channel
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Cell free-mtDNA release drives pyroptosis and inflammation in cell models carrying the mitochondrial m.3243A>G pathogenic variant
Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is primarily caused by the heteroplasmic m.3243A>G/MT-TL1 pathogenic variant. Patients exhibit elevated circulating cell-free mtDNA (cf-mtDNA) in plasma, which acts as a damage-associated molecular pattern. Using patient-derived fibroblasts and neuronal progenitors, as well as transmitochondrial cytoplasmic hybrids (cybrids), we show that mutant cells release higher levels of cf-mtDNA than wild-type...