Nix is a selective autophagy receptor for mitochondrial clearance.
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.
Novak
Ivana
I
Mediterranean Institute for Life Sciences, Mestrovicevo setaliste bb, HR-21000 Split, Croatia.
Kirkin
Vladimir
V
McEwan
David G
DG
Zhang
Ji
J
Wild
Philipp
P
Rozenknop
Alexis
A
Rogov
Vladimir
V
Löhr
Frank
F
Popovic
Doris
D
Occhipinti
Angelo
A
Reichert
Andreas S
AS
Terzic
Janos
J
Dötsch
Volker
V
Ney
Paul A
PA
Dikic
Ivan
I
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
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