PMID- 37621214
OWN - NLM
STAT- MEDLINE
DCOM- 20231116
LR  - 20231117
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 42
IP  - 22
DP  - 2023 Nov 15
TI  - Nix interacts with WIPI2 to induce mitophagy.
PG  - e113491
LID - 10.15252/embj.2023113491 [doi]
LID - e113491
AB  - Nix is a membrane-anchored outer mitochondrial protein that induces mitophagy. 
      While Nix has an LC3-interacting (LIR) motif that binds to ATG8 proteins, it also 
      contains a minimal essential region (MER) that induces mitophagy through an 
      unknown mechanism. We used chemically induced dimerization (CID) to probe the 
      mechanism of Nix-mediated mitophagy and found that both the LIR and MER are 
      required for robust mitophagy. We find that the Nix MER interacts with the 
      autophagy effector WIPI2 and recruits WIPI2 to mitochondria. The Nix LIR motif is 
      also required for robust mitophagy and converts a homogeneous WIPI2 distribution 
      on the surface of the mitochondria into puncta, even in the absence of ATG8s. 
      Together, this work reveals unanticipated mechanisms in Nix-induced mitophagy and 
      the elusive role of the MER, while also describing an interesting example of 
      autophagy induction that acts downstream of the canonical initiation complexes.
CI  - Published 2023. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Bunker, Eric N
AU  - Bunker EN
AUID- ORCID: 0000-0003-0368-9512
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD, USA.
FAU - Le Guerroue, Francois
AU  - Le Guerroue F
AUID- ORCID: 0000-0002-1982-1509
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD, USA.
FAU - Wang, Chunxin
AU  - Wang C
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD, USA.
FAU - Strub, Marie-Paule
AU  - Strub MP
AUID- ORCID: 0000-0003-4840-1893
AD  - Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, 
      National Institutes of Health, Bethesda, MD, USA.
FAU - Werner, Achim
AU  - Werner A
AUID- ORCID: 0000-0003-1051-8447
AD  - Stem Cell Biochemistry Unit, National Institute of Dental and Craniofacial 
      Research, National Institutes of Health, Bethesda, MD, USA.
FAU - Tjandra, Nico
AU  - Tjandra N
AD  - Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, 
      National Institutes of Health, Bethesda, MD, USA.
FAU - Youle, Richard J
AU  - Youle RJ
AUID- ORCID: 0000-0001-9117-5241
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, MD, USA.
LA  - eng
GR  - HHS|NIH|National Institute of Dental and Craniofacial Research (NIDCR)/
GR  - HHS|NIH|National Institute of Neurological Disorders and Stroke (NINDS)/
GR  - HHS|NIH|NHLBI|NHLBI Division of Intramural Research (DIR)/
PT  - Journal Article
DEP - 20230825
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Membrane Proteins)
RN  - 0 (Autophagy-Related Protein 8 Family)
RN  - 0 (Mitochondrial Proteins)
SB  - IM
MH  - *Mitophagy
MH  - *Autophagy
MH  - Mitochondria/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Autophagy-Related Protein 8 Family/metabolism
MH  - Mitochondrial Proteins/genetics/metabolism
PMC - PMC10646555
OTO - NOTNLM
OT  - Autophagy
OT  - BNIP3
OT  - FIP200
OT  - LIR
OT  - p62
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2023/08/25 06:43
MHDA- 2023/11/16 06:45
PMCR- 2024/08/25
CRDT- 2023/08/25 03:32
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/01/12 00:00 [received]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2024/08/25 00:00 [pmc-release]
PHST- 2023/11/16 06:45 [medline]
PHST- 2023/08/25 06:43 [pubmed]
PHST- 2023/08/25 03:32 [entrez]
AID - EMBJ2023113491 [pii]
AID - 10.15252/embj.2023113491 [doi]
PST - ppublish
SO  - EMBO J. 2023 Nov 15;42(22):e113491. doi: 10.15252/embj.2023113491. Epub 2023 Aug 
      25.