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Nix is a selective autophagy receptor for mitochondrial clearance
Authors:Ji Zhang  Philipp Wild  Alexis Rozenknop  Vladimir Rogov  Frank Löhr  Doris Popovic  Angelo Occhipinti  Andreas S Reichert  Janos Terzic  Volker Dötsch  Paul A Ney  Ivan Dikic
Institution:1. Department of Biochemistry, St Jude Children's Research Hospital, Memphis, Tennesse, 38105 USA;2. Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor‐Stern‐Kai 7, Frankfurt am Main, D‐60590 Germany;3. Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Marie Curie Strasse 9, Frankfurt am Main, D‐60439 Germany;4. Institute of Protein Research, Puschino, 142290 Russia;5. Mediterranean Institute for Life Sciences, Mestrovicevo setaliste bb, HR‐21000 Split, Croatia;6. Mitochondrial Biology, Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor‐Stern‐Kai 7, Frankfurt am Main, D‐60590 Germany;7. School of Medicine, University of Split, Soltanska 2, HR‐21000 Split, Croatia
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.
Keywords:GABARAP  LC3  mitophagy  Nix  selective autophagy
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