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Cited by 382

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics

Open access
Irrcher, I., Aleyasin, H., Seifert, E.L., Hewitt, S.J., Chhabra, S., Phillips, M., Lutz, A.K., Rousseaux, M.W.C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J.G., Winklhofer, K.F., Rizzu, P., Rippstein, P., Kim, R.H., Chen, C.X., Fon, E.A., Slack, R.S., Harper, M.E., McBride, H.M., Mak, T.W., Park, D.S.·2010·Human Molecular Genetics
DOI 10.1093/hmg/ddq288
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Abstract

Growing evidence highlights a role for mitochondrial dysfunction and oxidative stress as underlying contributors to Parkinson's disease (PD) pathogenesis. DJ-1 (PARK7) is a recently identified recessive familial PD gene. Its loss leads to increased susceptibility of neurons to oxidative stress and death. However, its mechanism of action is not fully understood. Presently, we report that DJ-1 deficiency in cell lines, cultured neurons, mouse brain and lymphoblast cells derived from DJ-1 patients display aberrant mitochondrial morphology. We also show that these DJ-1-dependent mitochondrial defects contribute to oxidative stress-induced sensitivity to cell death since reversal of this fragmented mitochondrial phenotype abrogates neuronal cell death. Reactive oxygen species (ROS) appear to play a critical role in the observed defects, as ROS scavengers rescue the phenotype and mitochondria isolated from DJ-1 deficient animals produce more ROS compared with control. Importantly, the aberrant mitochondrial phenotype can be rescued by the expression of Pink1 and Parkin, two PD-linked genes involved in regulating mitochondrial dynamics and quality control. Finally, we show that DJ-1 deficiency leads to altered autophagy in murine and human cells. Our findings define a mechanism by which the DJ-1-dependent mitochondrial defects contribute to the increased sensitivity to oxidative stress-induced cell death that has been previously reported.

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Metadata

Authors
Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., Winklhofer, K. F., Rizzu, P., Rippstein, P., Kim, R. H., Chen, C. X., Fon, E. A., Slack, R. S., Harper, M. E., McBride, H. M., Mak, T. W., & Park, D. S.
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2010-07-16
Volume
19
Issue
19
Pages
3734-3746
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddq288
OpenAlex
W2141918542
Cited by
382
References
16
FWCI
19.80
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. https://app.cochat.ai/papers/10.1093/hmg/ddq288
The paper
Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., Winklhofer, K. F., Rizzu, P., Rippstein, P., Kim, R. H., Chen, C. X., Fon, E. A., Slack, R. S., . . . Park, D. S. (2010). Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddq288

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

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.