Elevated serum mitochondrial DNA in females and lack of altered platelet mitochondrial methylation in patients with Parkinson´s disease

Abstract

Purpose: Mitochondrial dysfunction has long been considered in the pathogenesis of Parkinson's disease (PD). This is evident from the presence of mitochondrial DNA deletions in substantia nigra neurons and respiratory chain abnormalities in the skeletal muscle of PD patients. However, the contributing factors that potentially cause oxidative stress in PD are still elusive. To a certain extent, the identification of acquired changes in circulating mitochondrial DNA (mtDNA) content in blood samples may mirror the mitochondrial (dys-) function. Therefore, herein, we investigated the mtDNA concentrations in serum and cerebrospinal fluid (CSF) of PD patients.

Materials and methods: We performed quantitative analysis (qPCR) at two mitochondrial regions (D-Loop; ATPase6) and evaluated the platelet mtDNA methylation levels (MT-TL1 ,MT-CO1, MT-CO2 and MT-CO3) by bisulfite-PCR pyrosequencing.

Results: Our quantitative analysis at two mitochondrial regions (D-Loop; ATPase6) revealed an increase in mtDNA serum concentrations in PD females compared to healthy females. Of particular interest, these altered concentrations were restricted to females serum only. Thus, in males as well as CSF of PD patients no increase was detected. Additionally, mtDNA methylation in platelets isolated from the plasma of PD patients showed no altered methylation levels in the mitochondrial MT-TL1 and MT-CO1 regions. Besides, a complete lack of platelet mtDNA methylation was observed at MT-CO2 and MT-CO3 mitochondrial sites.

Conclusions: Taken together, we found an increased mtDNA serum concentration exclusively in PD females. As of yet, it is unclear whether this might reflect specific changes or characteristics of female PD pathobiology. However, in context to the ongoing debate about mtDNA methylation, we could show that the mitochondrial epigenome does harbor detectable CpG methylation sites in platelets-derived DNA.

Keywords:

• Parkinson´s diseases
• mitochondrial
• DNA methylation
• biomarkers
• Platelets

Acknowledgments

We thank all the patients who participated in this study. We also thank Sabine Proske-Schmitz and Samra Alijagic for technical support. The study was supported by the German Federal Ministry of Education and Research (BMBF/ANR) through the EpiPD (Epigenomics of Parkinson’s disease) project, under the auspices of the bilateral Epigenomics of Common and Age-related Diseases Programme (grant # 01KU1403B; UW). Simon Schaefer received a research grant from the WIFOMED foundation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was supported by the German Federal Ministry of Education and Research (BMBF/ANR) through the EpiPD (Epigenomics of Parkinson’s disease) project, under the auspices of the bilateral Epigenomics of Common and Age-related Diseases Programme (grant # 01KU1403B; UW)