title: Characterizing the mitochondrial DNA polymerase gamma interactome by BioID identifies Ruvbl2 localizes to the mitochondria.
abstract: Human mitochondrial DNA (mtDNA) is replicated by the mitochondrial DNA polymerase gamma (POLG). Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondrial localization for this protein. Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells. Additionally, transgenic overexpression of Ruvbl2 from an alternative translation initiation site resulted in mitochondrial co-localization. Overall, POLG interactome mapping identifies novel proteins which support mitochondrial biogenesis and a potential novel mitochondrial isoform of Ruvbl2.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, ON, Canada.
authors.forename: Sanduni U
authors.initials: SU
authors.lastname: Liyanage
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Coyaud
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Estelle M N
authors.initials: EM
authors.lastname: Laurent
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Rose
authors.initials: R
authors.lastname: Hurren
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Maclean
authors.affiliation: Medical Research Council, Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Wood
authors.affiliation: Medical Research Council, Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kazak
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Aisha
authors.initials: A
authors.lastname: Shamas-Din
authors.affiliation: Medical Research Council, Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Holt
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, ON, Canada. Electronic address: aaron.schimmer@utoronto.ca.
authors.forename: Aaron
authors.initials: A
authors.lastname: Schimmer
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000032:analysis*; D004265:DNA Helicases / Q000032:analysis*; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000737:chemistry*; D025941:Protein Interaction Mapping
chemical_list: D002352:Carrier Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human
keywords: BioID; Co-localization; Nucleoid; POLG; Ruvbl2; mtDNA