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
-
- Sequestosome-1 Protein/metabolism
- Membrane Proteins/metabolism*
- Mitophagy/physiology*
- Protein Binding
- Zebrafish Proteins/metabolism*
- Ubiquitin-Protein Ligases/metabolism
- Mitochondria/metabolism
- Transcription Factors/metabolism
- Mitochondrial Proteins/metabolism
- Autophagy-Related Protein 8 Family/metabolism
- Animals
- Zebrafish
- Neurons/metabolism
- Intracellular Signaling Peptides and Proteins/metabolism*
- RNA-Binding Proteins/metabolism
- Autophagy/physiology
- Carrier Proteins/metabolism
- Adaptor Proteins, Signal Transducing/metabolism
- Microtubule-Associated Proteins/metabolism
- Humans
- HeLa Cells
- Intercellular Signaling Peptides and Proteins/metabolism*
- HEK293 Cells
- PubMed
- 30982665 Full text @ Dev. Cell
Citation
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. (2019) NIPSNAP1 and NIPSNAP2 Act as "Eat Me" Signals for Mitophagy. Developmental Cell. 49(4):509-525.e12.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping