A yeast model of the Parkinson's disease-associated protein Parkin.
Mutations in Parkin, an E3 ubiquitin ligase, are associated to autosomal recessive Parkinson's disease (PD). Parkin has been mainly implicated, along with Pink1, in mitochondrial autophagy in response to stress. In this study, a yeast model was developed to analyse the biological function of human Parkin. We observed that Parkin increases yeast chronological lifespan and oxidative stress resistance, through a mitochondrial-dependent pathway. Moreover, in response to H2O2, Parkin translocate to mitochondria, leading to a higher mitochondrial degradation. Parkin-induced H2O2 resistance is dependent on the autophagic pathway and on the mitochondrial protein Por1p. Although expression of Pink1 induces an H2O2 resistance phenotype similar to Parkin, co-expression of both proteins does not result in a synergistic effect. Concerning H2O2 resistance, this may indicate that these two proteins independently affect the same pathway. Altogether, this work establishes a yeast model for Parkin, which may provide new insights on Parkin function and potential mechanisms of pathogenicity.
UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: clarafrancisco@gmail.com.
Clara
C
Pereira
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Vitor
V
Costa
Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester, United Kingdom.
L Miguel
LM
Martins
UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: lucilia.saraiva@ff.up.pt.
Lucília
L
Saraiva
D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
D016877:Oxidants; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D006861:Hydrogen Peroxide; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
Mitochondria; Parkin; Parkinson׳s disease; Pink1; Stress resistance; Yeast