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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Autophagy / physiology*
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Autophagy-Related Protein 8 Family
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Binding Sites
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Blotting, Western
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COS Cells
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Cells, Cultured
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Chlorocebus aethiops
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Mitochondria / metabolism*
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Mitochondrial Proteins / chemistry
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism*
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Molecular Sequence Data
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Protein Binding
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Receptors, GABA-A / metabolism
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Reticulocytes / cytology
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Substrate Specificity
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Ubiquitin-Protein Ligases / metabolism
Substances
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ATG8 protein, S cerevisiae
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Autophagy-Related Protein 8 Family
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BNIP3L protein, human
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MAP1LC3A protein, human
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Membrane Proteins
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Microtubule-Associated Proteins
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Mitochondrial Proteins
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Nix protein, mouse
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Proto-Oncogene Proteins
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Receptors, GABA-A
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases