Objective: Evaluate mitochondrial integrity in cultivated fibroblasts of patients with idiopathic Parkinson’s disease (IPD) and healthy controls (HC).

Background: Mitochondrial dysfunction (MD) is considered an essential contributor to IPD pathophysiology and could become a future treatment target. Although MD is probably not limited to the basal ganglia, studies on other tissues have so far produced conflicting data. We had initiated a three cell type evaluation of MD covering platelets (doi:10.1002/acn3.151), submucosal enteric ganglia neurons (doi:10.1038/srep33117), and fibroblasts. Here, we report the results in IPD fibroblasts.

Methods: 41 IPD patients (mean disease duration: 6.5 years (st.dev. 5.5 years) and 21 healthy age-matched controls were recruited. Punch skin biopsy was performed and mitochondrial membrane potential (Ψm) was measured via TMRM assay and automated microscopy before and after challenging with the protonophore FCCP.

Results: [figure1] Mitochondrial challenge test: (A) pooled single cell data histograms, (B) individually averaged data At single cell level, basal Ψm is significantly higher in IPD than in HC (p<0.001). Under FCCP stress, the median cellular Ψm per person is also significantly increased in IPD patients.

Conclusions: The fibroblasts of IPD patients show increased mitochondrial membrane potential both at the basal state and after challenging with a potent protonophore. These findings are counterintuitive at first look but may reflect compensatory mechanisms upstream of mitochondrial quality control. Indeed, the maintenance of mitochondrial membrane potential could prevent the triggering of mitochondrial degradation via the lysosomal pathway.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/challenging-mitochondria-in-idiopathic-parkinsons-disease-fibroblasts/