PUBLICATION

NIPSNAP1 and NIPSNAP2 Act as "Eat Me" Signals for Mitophagy

Authors
Princely Abudu, Y., Pankiv, S., Mathai, B.J., Håkon Lystad, A., Bindesbøll, C., Brenne, H.B., Yoke Wui Ng, M., Thiede, B., Yamamoto, A., Mutugi Nthiga, T., Lamark, T., Esguerra, C.V., Johansen, T., Simonsen, A.
ID
ZDB-PUB-190416-9
Date
2019
Source
Developmental Cell   49(4): 509-525.e12 (Journal)
Registered Authors
Esguerra, Camila V., Johansen, Terje
Keywords
ALFY, NDP52, NIPSNAP1, NIPSNAP2, Parkin, TAX1BP1, autophagy, mitophagy, optineurin, p62/SQSTM1
MeSH Terms
  • Protein Binding
  • Mitophagy/physiology*
  • Carrier Proteins/metabolism
  • Autophagy/physiology
  • Transcription Factors/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism
  • Autophagy-Related Protein 8 Family/metabolism
  • Ubiquitin-Protein Ligases/metabolism
  • Humans
  • RNA-Binding Proteins/metabolism
  • Zebrafish
  • Mitochondrial Proteins/metabolism
  • HEK293 Cells
  • Neurons/metabolism
  • HeLa Cells
  • Zebrafish Proteins/metabolism*
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Mitochondria/metabolism
  • Sequestosome-1 Protein/metabolism
  • Membrane Proteins/metabolism*
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Microtubule-Associated Proteins/metabolism
  • Animals
(all 23)
PubMed
30982665 Full text @ Dev. Cell
Abstract
The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) and NIPSNAP2 accumulate on the mitochondria surface upon mitochondrial depolarization. There, they recruit proteins involved in selective autophagy, including autophagy receptors and ATG8 proteins, thereby functioning as an "eat me" signal for mitophagy. NIPSNAP1 and NIPSNAP2 have a redundant function in mitophagy and are predominantly expressed in different tissues. Zebrafish lacking a functional Nipsnap1 display reduced mitophagy in the brain and parkinsonian phenotypes, including loss of tyrosine hydroxylase (Th1)-positive dopaminergic (DA) neurons, reduced motor activity, and increased oxidative stress.
Genes / Markers
Figures
Figure Gallery (2 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sa14357
    Point Mutation
    uio1TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      Sequence Targeting Reagents
      1 - 3 of 3
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      Fish
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-nipsnap1polyclonalIgGRabbit
      Ab1-nipsnap2polyclonalIgGRabbit
      Ab1-thmonoclonalIgG1Mouse
      Ab2-tubamonoclonal
        IgG1Mouse
        1 - 4 of 4
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        Orthology
        Gene Orthology
        nipsnap1
        nipsnap2
        1 - 2 of 2
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        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        mCherryEFGmCherry
        1 - 2 of 2
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        Mapping
        No data available