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Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression

Overview of attention for article published in Neurobiology of Disease, October 2013
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Title
Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression
Published in
Neurobiology of Disease, October 2013
DOI 10.1016/j.nbd.2013.10.021
Pubmed ID
Authors

Rubén Gómez-Sánchez, Matthew E. Gegg, José M. Bravo-San Pedro, Mireia Niso-Santano, Lydia Alvarez-Erviti, Elisa Pizarro-Estrella, Yolanda Gutiérrez-Martín, Alberto Alvarez-Barrientos, José M. Fuentes, Rosa Ana González-Polo, Anthony H.V. Schapira

Abstract

Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection.

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The data shown below were compiled from readership statistics for 120 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
India 1 <1%
United States 1 <1%
Germany 1 <1%
Unknown 116 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 30 25%
Researcher 26 22%
Student > Master 18 15%
Student > Bachelor 7 6%
Student > Postgraduate 5 4%
Other 15 13%
Unknown 19 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 31 26%
Biochemistry, Genetics and Molecular Biology 27 23%
Neuroscience 17 14%
Medicine and Dentistry 15 13%
Pharmacology, Toxicology and Pharmaceutical Science 4 3%
Other 7 6%
Unknown 19 16%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 September 2014.
All research outputs
#22,759,802
of 25,374,917 outputs
Outputs from Neurobiology of Disease
#3,133
of 3,389 outputs
Outputs of similar age
#199,268
of 225,434 outputs
Outputs of similar age from Neurobiology of Disease
#42
of 45 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
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