The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Mutant A53T α-Synuclein Induces Neuronal Death by Increasing Mitochondrial Autophagy
Open accessAbstract
Parkinson disease is characterized by the accumulation of aggregated α-synuclein as the major component of the Lewy bodies. α-Synuclein accumulation in turn leads to compensatory effects that may include the up-regulation of autophagy. Another common feature of Parkinson disease (PD) is mitochondrial dysfunction. Here, we provide evidence that the overactivation of autophagy may be a link that connects the intracellular accumulation of α-synuclein with mitochondrial dysfunction. We found that the activation of macroautophagy in primary cortical neurons that overexpress mutant A53T α-synuclein leads to massive mitochondrial destruction and loss, which is associated with a bioenergetic deficit and neuronal degeneration. No mitochondrial removal or net loss was observed when we suppressed the targeting of mitochondria to autophagosomes by silencing Parkin, overexpressing wild-type Mitofusin 2 and dominant negative Dynamin-related protein 1 or blocking autophagy by silencing autophagy-related genes. The inhibition of targeting mitochondria to autophagosomes or autophagy was also partially protective against mutant A53T α-synuclein-induced neuronal cell death. These data suggest that overactivated mitochondrial removal could be one of the contributing factors that leads to the mitochondrial loss observed in PD models.
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Citations
Cites
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
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PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835
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Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
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PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624
PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616
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α-Synuclein Is Degraded by Both Autophagy and the Proteasome
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Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
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Cited by
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897
Understanding Dopaminergic Cell Death Pathways in Parkinson Disease
Michel, P. P., Hirsch, E. C., & Hunot, S. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.038 · Cited by 600
Metadata
- Authors
- Choubey, V., Safiulina, D., Vaarmann, A., Cagalinec, M., Wareski, P., Kuum, M., Zharkovsky, A., & Kaasik, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 12
- Pages
- 10814-10824
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1990294498
- Cited by
- 262
- References
- 13
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Choubey, V., Safiulina, D., Vaarmann, A., Cagalinec, M., Wareski, P., Kuum, M., Zharkovsky, A., & Kaasik, A. (2011). Mutant A53T α-Synuclein Induces Neuronal Death by Increasing Mitochondrial Autophagy. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.132514
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
