PUBLICATION

NIPSNAP1 and NIPSNAP2 act as "eat me" signals to allow sustained recruitment of autophagy receptors during mitophagy

Authors
Abudu, Y.P., Pankiv, S., Mathai, B.J., Lamark, T., Johansen, T., Simonsen, A.
ID
ZDB-PUB-190701-14
Date
2019
Source
Autophagy   15(10): 1845-1847 (Journal)
Registered Authors
Johansen, Terje
Keywords
Atg8, NIPSNAP1, NIPSNAP2, PINK1/Parkin, SLRs, mitophagy, “eat me” signal
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Autophagy
  • Autophagy-Related Protein 8 Family/genetics
  • Autophagy-Related Protein 8 Family/metabolism
  • Autophagy-Related Proteins/metabolism*
  • Gene Knockout Techniques
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins/physiology*
  • Intracellular Signaling Peptides and Proteins/physiology*
  • Membrane Proteins/physiology*
  • Mitophagy/genetics*
  • Protein Binding
  • Sequestosome-1 Protein/chemistry
  • Sequestosome-1 Protein/metabolism
  • Signal Transduction/genetics
  • Zebrafish
PubMed
31251109 Full text @ Autophagy
Abstract
Removal of damaged mitochondria is vital for cellular homeostasis especially in non-dividing cells, like neurons. Damaged mitochondria that cannot be repaired by the ubiquitin-proteasomal system are cleared by a form of selective autophagy known as mitophagy. Following damage, mitochondria become labelled with "eat-me" signals that selectively determine their degradation. Recently, we identified the mitochondrial matrix proteins, NIPSNAP1 (nipsnap homolog 1) and NIPSNAP2 as "eat-me" signals for damaged mitochondria. NIPSNAP1 and NIPSNAP2 accumulate on the mitochondrial outer membrane following mitochondrial depolarization, recruiting autophagy receptors and adaptors, as well as human Atg8 (autophagy-related 8)-family proteins to facilitate mitophagy. The NIPSNAPs allow a sustained recruitment of SQSTM1-like receptors (SLRs) to ensure efficient mitophagy. Zebrafish lacking Nipsnap1 show decreased mitophagy in the brain coupled with increased ROS production, loss of dopaminergic neurons and strongly reduced locomotion.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping