Cited by 1,309Autophagy in Disease and TherapyUbiquitin and proteasome pathwaysCalcium signaling and nucleotide metabolism

Nix is a selective autophagy receptor for mitochondrial clearance

Open access
Novak, Ivana, Kirkin, Vladimir, McEwan, David G, Zhang, Ji, Wild, Philipp, Rozenknop, Alexis, Rogov, Vladimir, Löhr, Frank +7 more·2010·The EMBO Reports

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.

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Authors
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., Reichert, A. S., Terzic, J., Dötsch, V., Ney, P. A., & Dikic, I.
Affiliations
  • Mediterranean Institute for Life Sciences (HR)
  • Goethe University Frankfurt (DE)
  • St. Jude Children's Research Hospital (US)
Venue
The EMBO Reports
Published
2009-12-11
Volume
11
Issue
1
Pages
45-51
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
OpenAlex
W2127440157
Cited by
1,309
References
35
Citations by year
2026: 63 · 2025: 77 · 2024: 79 · 2023: 72 · 2022: 81 · 2021: 106 · 2020: 96 · 2019: 86 · 2018: 77 · 2017: 74 · 2016: 85 · 2015: 72 · 2014: 77 · 2013: 63 · 2012: 90
FWCI
44.76
Type
journal article
Language
en
Open access
Locations
  • EMBO Reports (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft ((EXC 115).)
  • Terry Fox Foundation
  • National Institutes of Health (CA21765))
  • National Cancer Institute (P 30CA 21765, P30CA021765)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK074519, R21DK074519)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
Nix, selective autophagy, mitophagy, autophagy receptors, LC3, GABARAP, LC3-interacting region, mitochondrial clearance, mitochondrial damage, reticulocytes, erythroid differentiation, ubiquitin-like proteins
MeSH terms
Autophagy-Related Protein 8 Family, Amino Acid Sequence, Animals, Autophagy, Binding Sites, Cells, Cultured, Chlorocebus aethiops, Humans, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Molecular Sequence Data, Protein Binding, Proto-Oncogene Proteins, Receptors, GABA-A, Reticulocytes, Substrate Specificity, Blotting, Western, COS Cells, Amino Acid Motifs, Mitochondrial Proteins, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases, Mice

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