title: Nix is a selective autophagy receptor for mitochondrial clearance.
abstract: Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. Here, we show that the mitochondrial protein Nix is a selective autophagy receptor by binding to LC3/GABARAP proteins, ubiquitin-like modifiers that are required for the growth of autophagosomal membranes. In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region. Furthermore, ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation.
authors.affiliation: Mediterranean Institute for Life Sciences, Mestrovicevo setaliste bb, HR-21000 Split, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Novak
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kirkin
authors.forename: David G
authors.initials: DG
authors.lastname: McEwan
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Philipp
authors.initials: P
authors.lastname: Wild
authors.forename: Alexis
authors.initials: A
authors.lastname: Rozenknop
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rogov
authors.forename: Frank
authors.initials: F
authors.lastname: Löhr
authors.forename: Doris
authors.initials: D
authors.lastname: Popovic
authors.forename: Angelo
authors.initials: A
authors.lastname: Occhipinti
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
authors.forename: Janos
authors.initials: J
authors.lastname: Terzic
authors.forename: Volker
authors.initials: V
authors.lastname: Dötsch
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ney
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D012156:Reticulocytes / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; C116838:BNIP3L protein, human; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C501741:Nix protein, mouse; D011518:Proto-Oncogene Proteins; D011963:Receptors, GABA-A; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases