Hypoxia-induced LONP1 overexpression and mtDNA damage may serve as biomarkers for death from mechanical asphyxia.

Due to the absence of reliable signs, the authentication of death from mechanical asphyxia (DMA), commonly seen in forensic pathology, can be rather challenging especially when the criminal case is obscure. Lon protease-1 (LONP1) is an ATP-dependent serine protease located in mitochondria that participates in maintaining the integrity of the mitochondrial genome and regulating mitochondrial DNA (mtDNA) replication. In this research, cerebral tissues of corpses with different causes of death were collected to compare the expression of LONP1 and the changes of mtDNA to see the authenticating value of these markers. It was found that LONP1 was up-regulated in the cerebral tissue of DMA corpses while the integrity of mtDNA was destroyed conditionally. In neuroblastoma cancer cell line SH-SY5Y, LONP1 would suppress the repair and replication of mtDNA under hypoxia and partly lead to mitochondrial damage. In general, LONP1 is responsible for longer duration of hypoxic mtDNA damage and the repression of the replication of mtDNA. LONP1 and mtDNA integrity can both serve as biomarkers for DMA.