title: NBR1 is dispensable for PARK2-mediated mitophagy regardless of the presence or absence of SQSTM1.
abstract: Degradation of malfunctional mitochondria by mitophagy is a pivotal component of mitochondrial quality control to maintain cellular homeostasis. Mitochondrial clearance through the PINK1/PARK2 pathway is mediated by autophagic adaptor proteins. Previous studies revealed a significant involvement, but not an absolute requirement for SQSTM1 in PARK2-dependent mitophagy, suggesting that the existence of redundant adaptor proteins may compensate for the loss of SQSTM1. Here we investigated whether NBR1, a functional homolog of SQSTM1, has a role in PARK2-mediated mitophagy, either alone or as a compensatory mechanism. We showed that NBR1 does not appear to be required for mitochondrial clustering following mitochondrial depolarization. Moreover, we demonstrated that deletion of NBR1 alone or in combination with SQSTM1 does not prevent the degradation of damaged mitochondria. Our data suggest that NBR1 is dispensable for PARK2-dependent mitophagy and additional autophagic adaptor proteins, other than NBR1, are responsible for mitochondrial degradation in cells depleted of SQSTM1.
authors.affiliation: Department of Pathology and Laboratory Medicine, James Hogg Research Center, Providence Heart+Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pathology and Laboratory Medicine, James Hogg Research Center, Providence Heart+Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Fung
authors.affiliation: Department of Pathology and Laboratory Medicine, James Hogg Research Center, Providence Heart+Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Pathology and Laboratory Medicine, James Hogg Research Center, Providence Heart+Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.|Mayo Graduate School, Neurobiology of Disease, Jacksonville, FL, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Fiesel
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.|Mayo Graduate School, Neurobiology of Disease, Jacksonville, FL, USA.
authors.forename: W
authors.initials: W
authors.lastname: Springer
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, China.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, James Hogg Research Center, Providence Heart+Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D063306:Mitophagy / Q000187:drug effects / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071456:Sequestosome-1 Protein; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein