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Hypoxia-induced LONP1 overexpression and mtDNA damage may serve as biomarkers for death from mechanical asphyxia
Tianpu Wu1, Heng Zhang2, Dongchuan Zhang3
1Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; School of Forensic Medicine and Science, Fudan University, Shanghai 200032, China.
Abstract:
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.
Insights
Authentication of death from mechanical asphyxia (DMA) is challenging. New research shows Lon protease-1 (LONP1) and mitochondrial DNA (mtDNA) integrity can serve as reliable biomarkers for DMA.
Area of Science:
- Forensic Pathology
- Biochemistry
- Molecular Biology
Background:
- Mechanical asphyxia deaths present diagnostic challenges in forensic pathology due to a lack of definitive markers.
- Mitochondrial dysfunction and DNA integrity are increasingly recognized as indicators of cellular stress and damage.
Purpose of the Study:
- To investigate the potential of Lon protease-1 (LONP1) expression and mitochondrial DNA (mtDNA) integrity as biomarkers for death from mechanical asphyxia (DMA).
- To explore the role of LONP1 in regulating mtDNA integrity under hypoxic conditions relevant to asphyxia.
Main Methods:
- Comparative analysis of cerebral tissues from deceased individuals with varying causes of death.
- Assessment of LONP1 protein expression levels.
- Evaluation of mitochondrial DNA (mtDNA) integrity.
- In vitro studies using SH-SY5Y neuroblastoma cells under hypoxic conditions.
Main Results:
- LONP1 expression was significantly upregulated in the cerebral tissues of individuals who died from DMA.
- mtDNA integrity was found to be conditionally compromised in DMA cases.
- In vitro, LONP1 suppressed mtDNA repair and replication under hypoxia, contributing to mitochondrial damage.
Conclusions:
- Both LONP1 and mtDNA integrity show promise as reliable biomarkers for the authentication of death from mechanical asphyxia (DMA).
- LONP1 plays a role in exacerbating hypoxic mtDNA damage and inhibiting mtDNA replication, highlighting its significance in asphyxial events.
