| Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson's subject mitochondrial transfer. | |
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MedLine Citation:
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PMID: 20132468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Parkinson's disease (PD) is associated with perturbed mitochondrial function. Studies of cytoplasmic hybrid (cybrid) cell lines containing mitochondria from PD subjects suggest complex I dysfunction in particular is a relatively upstream biochemical defect. To evaluate potential downstream consequences of PD mitochondrial dysfunction, we used a cybrid approach to model PD mitochondrial dysfunction; our cybrid cell lines were generated via transfer of PD or control subject platelet mitochondria to mtDNA-depleted NT2 cells. To confirm our PD cybrid mitochondria did indeed differ from control cybrid mitochondria we measured complex I V(max) activities. Consistent with other PD cybrid reports, relative to control cybrid cell lines the PD cybrid cell line mean complex I V(max) activity was reduced. In this validated model, we used an oxygen electrode to characterize PD cybrid mitochondrial respiration. Although whole cell basal oxygen consumption was comparable between the PD and control cybrid groups, the proton leak was increased and maximum respiratory capacity was decreased in the PD cybrids. PD cybrids also had reduced SIRT1 phosphorylation, reduced peroxisome proliferator-activated receptor-gamma coactivator-1alpha levels, and increased NF-kB activation. We conclude mitochondrial respiration and pathways influenced by aerobic metabolism are altered in NT2 cybrid cell lines generated through transfer of PD subject platelet mitochondria. |
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Authors:
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A Raquel Esteves; Jane Lu; Mariana Rodova; Isaac Onyango; E Lezi; Richard Dubinsky; Kelly E Lyons; Rajesh Pahwa; Jeffrey M Burns; Sandra M Cardoso; Russell H Swerdlow |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-01 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 113 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-16 Completed Date: 2010-05-04 Revised Date: 2010-07-06 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 674-82 Citation Subset: IM |
Affiliation:
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Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aerobiosis
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physiology Aged Anaerobiosis / physiology Blotting, Western Cell Line Cell Respiration / physiology Citrate (si)-Synthase / metabolism Electron Transport Complex I / metabolism Enzyme Activation / physiology Humans Hybrid Cells Kinetics Middle Aged Mitochondria / enzymology, metabolism* NF-kappa B / metabolism Oxygen Consumption / physiology* Parkinson Disease / metabolism*, pathology Protons Sirtuin 1 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/Protons; EC 1.6.5.3/Electron Transport Complex I; EC 2.3.3.1/Citrate (si)-Synthase; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirtuin 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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