title: A new split-GFP-based probe reveals DJ-1 translocation into the mitochondrial matrix to sustain ATP synthesis upon nutrient deprivation.
abstract: The Parkinson's disease-related protein DJ-1 has a role in the protection against oxidative stress and maintenance of mitochondria structure. Whether this action depends on its localization and activity within the mitochondria is not clear. Here we develop an approach to resolve intra-mitochondrial distribution of DJ-1 and monitor its translocation under specific conditions. By a new split-green fluorescent protein (GFP)-based tool, we can observe that a small DJ-1 fraction is located within the mitochondrial matrix and that it consistently increases upon nutrient depletion. We also find that the targeting of DJ-1 to the mitochondrial matrix enhances mitochondrial and cytosolic adenosine triphosphate levels. Intriguingly, DJ-1 pathogenic mutants fail to improve bioenergetics and translocate within the mitochondrial matrix, suggesting that the DJ-1 protective role requires both these actions. By this new split-GFP-based tool, we can resolve mitochondrial compartmentalization of proteins which are not constitutively resident in mitochondria but translocate to them in response to specific stimuli.
authors.affiliation: Department of Biology, University of Padova, Via U. Bassi, 58/b, 35131 Padova, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Calì
authors.affiliation: Department of Biology, University of Padova, Via U. Bassi, 58/b, 35131 Padova, Italy.
authors.forename: Denis
authors.initials: D
authors.lastname: Ottolini
authors.affiliation: Department of Biology, University of Padova, Via U. Bassi, 58/b, 35131 Padova, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Soriano
authors.affiliation: Department of Biology, University of Padova, Via U. Bassi, 58/b, 35131 Padova, Italy marisa.brini@unipd.it.
authors.forename: Marisa
authors.initials: M
authors.lastname: Brini
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D001343:Autophagy / Q000235:genetics; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D000071617:Protein Deglycase DJ-1; D021381:Protein Transport
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000255:Adenosine Triphosphate; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1