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Characterization of the potential role of myosin IIa in parkin translocation during mitopahgy Panelli , Patrizio 2015

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Title Characterization of the potential role of myosin IIa in parkin translocation during mitopahgy
Creator Panelli , Patrizio
Publisher University of British Columbia
Date Issued 2015
Description Mitochondria are important organelles of eukaryotic cells that provide energy through cellular respiration. Cells have evolved several quality control mechanisms to preserve functional mitochondria and avoid cell damage. Damaged mitochondria are recognized and removed by mitophagy to avoid the production of reactive oxygen species. A major signal for the recognition of damaged mitochondria is the electrical membrane potential depolarization, which leads to the recruitment of PTEN-induced putative kinase 1 (PINK1), followed by the recruitment of the E3 ubiquitin ligase parkin at the outer mitochondrial membrane. Parkin ubiquitinates numerous mitochondrial outer membrane proteins and initiates mitophagy. Mutations in the gene encoding parkin are frequently found in familiar forms of Parkinson’s disease. Although several factors involved in parkin mitochondrial recruitment have been characterized, additional proteins may be involved. The aim of this work was to determine whether other factors may be involved in colocalizing parkin to damaged mitochondria. Following up a SILAC-immunoprecipitation experiment, we hypothesized that an unconventional myosin (myosin IIa) may be involved in the recruitment of parkin to the mitochondria. Myosins are a large family of actin-based cytoskeletal motors that use energy derived from ATP hydrolysis to generate movement. Non-conventional myosins are well studied for their contribution to synaptic function in neuronal cells. MYH9 was identified as potential interactor of parkin by mass spectrometry. This interaction was validated through co-immunoprecipitation and immunofluorescence experiments. In addition, myosin alteration with small chemicals that depolymerize actin filament or inhibit myosin activity, impaired parkin localization to mitochondria upon stress. This study potentially implicates myosin IIa as a modulator of parkin recruitment to the mitochondria, and may thus open the door to new therapeutic strategies for Parkinson’s disease.
Genre Thesis/Dissertation
Type Text
Language eng
Date Available 2015-04-28
Provider Vancouver : University of British Columbia Library
Rights Attribution-NoDerivs 2.5 Canada
DOI 10.14288/1.0166262
URI http://hdl.handle.net/2429/52976
Degree Master of Science - MSc
Program Biochemistry and Molecular Biology
Affiliation Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Degree Grantor University of British Columbia
GraduationDate 2015-09
Campus UBCV
Scholarly Level Graduate
Rights URI http://creativecommons.org/licenses/by-nd/2.5/ca/
AggregatedSourceRepository DSpace

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