The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Mitochondrial Lipid Abnormality and Electron Transport Chain Impairment in Mice Lacking α-Synuclein
Open accessAbstract
The presynaptic protein alpha-synuclein, implicated in Parkinson disease (PD), binds phospholipids and has a role in brain fatty acid (FA) metabolism. In mice lacking alpha-synuclein (Snca-/-), total brain steady-state mass of the mitochondria-specific phospholipid, cardiolipin, is reduced 22% and its acyl side chains show a 51% increase in saturated FAs and a 25% reduction in essential n-6, but not n-3, polyunsaturated FAs. Additionally, 23% reduction in phosphatidylglycerol content, the immediate biosynthetic precursor of cardiolipin, was observed without alterations in the content of other brain phospholipids. Consistent with these changes, more ordered lipid head group and acyl chain packing with enhanced rotational motion of diphenylhexatriene (DPH) about its long axis were demonstrated in time-resolved DPH fluorescence lifetime experiments. These abnormalities in mitochondrial membrane properties were associated with a 15% reduction in linked complex I/III activity of the electron transport chain, without reductions in mitochondrial number, complex II/III activity, or individual complex I, II, III, or IV activity. Reduced complex I activity is thought to be a critical factor in the development of PD. Thus, altered membrane composition and structure and impaired complex I/III function in Snca-/- brain suggest a relationship between alpha-synuclein's role in brain lipid metabolism, mitochondrial function, and PD.
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Cites
Mitochondrial Complex I Deficiency in Parkinson's Disease
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Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722
Generation of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260
The biosynthesis and functional role of cardiolipin
Schlame, M., Rua, D., & Greenberg, M. L. (2000) · Progress in Lipid Research · doi:10.1016/s0163-7827(00)00005-9 · Cited by 810
Double-knockout mice for α- and β-synucleins: Effect on synaptic functions
Chandra, S., Fornai, F., Kwon, H.-B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406283101 · Cited by 438
Cited by
Devi, L., Raghavendran, V., Prabhu, B. M., Avadhani, N. G., & Anandatheerthavarada, H. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710012200 · Cited by 1,080
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Mitochondrial dysfunction in Parkinson's disease
Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688
Mitochondrial bioenergetics and structural network organization
Benard, G., Bellance, N., James, D., Parrone, P., Fernandez, H., Letellier, T., & Rossignol, R. (2007) · Journal of Cell Science · doi:10.1242/jcs.03381 · Cited by 618
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons
Ekstrand, M. I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F. S., Trifunovic, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605208103 · Cited by 605
Metadata
- Authors
- Ellis, C. E., Murphy, E. J., Mitchell, D. C., Golovko, M. Y., Scaglia, F., Barceló-Coblijn, G. C., & Nussbaum, R. L.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-11-01
- Volume
- 25
- Issue
- 22
- Pages
- 10190-10201
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2100872265
- Cited by
- 260
- References
- 5
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Ellis, C. E., Murphy, E. J., Mitchell, D. C., Golovko, M. Y., Scaglia, F., Barceló-Coblijn, G. C., & Nussbaum, R. L. (2005). Mitochondrial Lipid Abnormality and Electron Transport Chain Impairment in Mice Lacking α-Synuclein. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.25.22.10190-10201.2005
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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