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Cited by 373

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Loss of Parkin or PINK1 Function Increases Drp1-dependent Mitochondrial Fragmentation

Open access
Lutz, A. Kathrin, Exner, Nicole, Fett, Mareike E., Schlehe, Julia S., Kloos, Karina, Lämmermann, Kerstin, Brunner, Bettina, Kurz-Drexler, Annerose, Vogel, Frank, Reichert, Andreas S., Bouman, Lena, Vogt-Weisenhorn, Daniela, Wurst, Wolfgang, Tatzelt, Jörg, Haass, Christian, Winklhofer, Konstanze F.·2009·Journal of Biological Chemistry

Abstract

Loss-of-function mutations in the parkin gene (PARK2) and PINK1 gene (PARK6) are associated with autosomal recessive parkinsonism. PINK1 deficiency was recently linked to mitochondrial pathology in human cells and Drosophila melanogaster, which can be rescued by parkin, suggesting that both genes play a role in maintaining mitochondrial integrity. Here we demonstrate that an acute down-regulation of parkin in human SH-SY5Y cells severely affects mitochondrial morphology and function, a phenotype comparable with that induced by PINK1 deficiency. Alterations in both mitochondrial morphology and ATP production caused by either parkin or PINK1 loss of function could be rescued by the mitochondrial fusion proteins Mfn2 and OPA1 or by a dominant negative mutant of the fission protein Drp1. Both parkin and PINK1 were able to suppress mitochondrial fragmentation induced by Drp1. Moreover, in Drp1-deficient cells the parkin/PINK1 knockdown phenotype did not occur, indicating that mitochondrial alterations observed in parkin- or PINK1-deficient cells are associated with an increase in mitochondrial fission. Notably, mitochondrial fragmentation is an early phenomenon upon PINK1/parkin silencing that also occurs in primary mouse neurons and Drosophila S2 cells. We propose that the discrepant findings in adult flies can be explained by the time of phenotype analysis and suggest that in mammals different strategies may have evolved to cope with dysfunctional mitochondria.

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Metadata

Authors
Lutz, A. K., Exner, N., Fett, M. E., Schlehe, J. S., Kloos, K., Lämmermann, K., Brunner, B., Kurz-Drexler, A., Vogel, F., Reichert, A. S., Bouman, L., Vogt-Weisenhorn, D., Wurst, W., Tatzelt, J., Haass, C., & Winklhofer, K. F.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-08
Volume
284
Issue
34
Pages
22938-22951
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2172060930
Cited by
373
References
15
FWCI
22.50
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Loss of Parkin or PINK1 Function Increases Drp1-dependent Mitochondrial Fragmentation. https://app.cochat.ai/papers/10.1074/jbc.m109.035774
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Lutz, A. K., Exner, N., Fett, M. E., Schlehe, J. S., Kloos, K., Lämmermann, K., Brunner, B., Kurz-Drexler, A., Vogel, F., Reichert, A. S., Bouman, L., Vogt-Weisenhorn, D., Wurst, W., Tatzelt, J., Haass, C., & Winklhofer, K. F. (2009). Loss of Parkin or PINK1 Function Increases Drp1-dependent Mitochondrial Fragmentation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.035774

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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.