Objective: To determine whether structural and/or functional deficiencies of the mitochondrial respiratory chain (MRC) occur in the skeletal muscle of patients with idiopathic Parkinson’s disease (iPD) and assess its pervasiveness.
Background: Mitochondrial dysfunction is an established feature of the pathophysiology of iPD. However, its presence in peripheral tissues remains controversial. The clinical heterogeneity of iPD implies an underlying molecular heterogeneity, but molecular subtypes are yet to be discovered. We hypothesized that the variable results of previous studies assessing the MRC in iPD muscle may be due to interindividual variation, where MRC deficiency only occurs in a subgroup of iPD cases. Developing peripheral biomarkers of mitochondrial dysfunction in iPD would represent a major advance in the field, as it would allow for selection of patients for trials of targeted therapies.
Method: Needle biopsies of the vastus lateralis were collected from 76 patients with iPD and 15 neurologically healthy controls. Quantitative analysis of the MRC was conducted by immunofluorescence of muscle sections for complexes I and IV, as well as the mitochondrial mass marker VDAC1. MRC function was assessed by spectrophotometric specific activity assays of complexes I to IV. Analysis of mitochondrial DNA (mtDNA) was performed in a total of 158 single muscle fibers from 6 patients with iPD and 6 controls, using qPCR for copy number and deletion measurement and ultra-deep sequencing for point variation.
Results: Immunofluorescence revealed no quantitative change of complexes I or IV in single muscle fibers. However, activity assays showed a small but significant reduction in complex I specific activity in iPD compared to controls. mtDNA assessment is ongoing at the time of abstract submission.
Conclusion: These findings suggest that complex I activity, rather than quantity, should be explored as a peripheral tissue biomarker of mitochondrial dysfunction in idiopathic Parkinson’s disease.
To cite this abstract in AMA style:
S. Kverneng, K. Stige, H. Berven, S. Mostafavi, M. Brischigliaro, B. Brakedal, G. Skeie, G. Nido, I. Flønes, E. Fernandez-Vizarra, C. Dölle, C. Tzoulis. Impaired mitochondrial respiration as a peripheral tissue biomarker for stratifying idiopathic Parkinson’s disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/impaired-mitochondrial-respiration-as-a-peripheral-tissue-biomarker-for-stratifying-idiopathic-parkinsons-disease/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/impaired-mitochondrial-respiration-as-a-peripheral-tissue-biomarker-for-stratifying-idiopathic-parkinsons-disease/