title: Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects.
abstract: The E3 ubiquitin ligase PARK2 and the mitochondrial protein kinase PINK1 are required for the initiation of mitochondrial damage-induced mitophagy. Together, PARK2 and PINK1 generate a phospho-ubiquitin signal on outer mitochondrial membrane proteins that triggers recruitment of the autophagy machinery. This paper describes the detection of a defined 500-kDa phospho-ubiquitin-rich PARK2 complex that accumulates on mitochondria upon treatment with the membrane uncoupler CCCP. Formation of this complex is dependent on the presence of PINK1 and is absent in mutant forms of PARK2, whereby mitophagy is also arrested. These results signify a functional signaling complex that is essential for the progression of mitophagy. The visualization of the PARK2 signaling complex represents a novel marker for this critical step in mitophagy and can be used to monitor mitophagy progression in PARK2 mutants and to uncover additional upstream factors required for PARK2-mediated mitophagy signaling.
authors.affiliation: a Department of Cellular Biochemistry , University Medical Center Göttingen , Göttingen , Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Callegari
authors.affiliation: b University of Freiburg , Department of Biochemistry and Functional Proteomics , Institute of Biology II, Faculty of Biology , Freiburg , Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.affiliation: b University of Freiburg , Department of Biochemistry and Functional Proteomics , Institute of Biology II, Faculty of Biology , Freiburg , Germany.|c University of Freiburg, BIOSS Center for Biological Signaling Studies , Freiburg , Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: a Department of Cellular Biochemistry , University Medical Center Göttingen , Göttingen , Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Dennerlein
authors.affiliation: a Department of Cellular Biochemistry , University Medical Center Göttingen , Göttingen , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thumm
authors.affiliation: a Department of Cellular Biochemistry , University Medical Center Göttingen , Göttingen , Germany.|d Max Planck Institute for Biophysical Chemistry , Göttingen , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.affiliation: a Department of Cellular Biochemistry , University Medical Center Göttingen , Göttingen , Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dudek
mesh_terms: D001343:Autophagy; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D063306:Mitophagy; D009154:Mutation; D010766:Phosphorylation; D000072417:Protein Domains; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D007074:Immunoglobulin G; D024101:Mitochondrial Proteins; D011494:Protein Kinases; D034741:RNA, Small Interfering; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
keywords: E3 ubiquitin ligase; PARK2; PINK1; Parkin; Parkinson disease; autophagy; mitochondria; mitophagy; phospho-ubiquitin