Reduced DJ-1–F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
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Published version
Author(s)
Type
Journal Article
Abstract
Disruption in neuronal and synaptic metabolic homeostasis is a key driver of neurodegeneration in Parkinson’s disease (PD). Mitochondrial activity, biomass, and efficiency are critical to this balance. While activity and biomass are well-characterized in PD pathology, mitochondrial metabolic efficiency remains insufficiently explored. Our previous studies showed that the protein product of PD-associated gene DJ-1 modulates metabolic efficiency through its interaction with the F1Fo-ATP-synthase β-subunit (β-sub). Here, using proximity ligation assay (PLA), we compared
mitochondrial DJ-1–β-sub association in distinct mesencephalic dopaminergic (mesDA) neuronal
subpopulations and their intracellular compartments of PD and control post-mortem brains. In PD brains, DJ-1–β-sub-PLA was lower than control in substantia nigra pars compacta (SNpc) somata and neurites but unchanged in ventral tegmental area (VTA) neurons. In PD and control cases, the PLA signal was reduced in distal neurites of SNpc compared to VTA neurons. These intracellular and region-specific differences suggest that impaired mitochondrial efficiency may contribute to the differential vulnerability of mesDA neurons in PD.
mitochondrial DJ-1–β-sub association in distinct mesencephalic dopaminergic (mesDA) neuronal
subpopulations and their intracellular compartments of PD and control post-mortem brains. In PD brains, DJ-1–β-sub-PLA was lower than control in substantia nigra pars compacta (SNpc) somata and neurites but unchanged in ventral tegmental area (VTA) neurons. In PD and control cases, the PLA signal was reduced in distal neurites of SNpc compared to VTA neurons. These intracellular and region-specific differences suggest that impaired mitochondrial efficiency may contribute to the differential vulnerability of mesDA neurons in PD.
Date Issued
2025-06-01
Date Acceptance
2025-05-02
Citation
Science Advances, 2025, 11 (23)
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Journal / Book Title
Science Advances
Volume
11
Issue
23
Copyright Statement
© 2025 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
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Publication Status
Published
Date Publish Online
2025-06-06