PUBLICATION
Pregnancy associated plasma protein-aa regulates endoplasmic reticulum-mitochondria associations
- Authors
- Alassaf, M., Halloran, M.C.
- ID
- ZDB-PUB-210325-10
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Halloran, Mary
- Keywords
- cell biology, neuroscience, zebrafish
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Endoplasmic Reticulum/metabolism*
- Endoplasmic Reticulum Stress/physiology*
- Hair Cells, Auditory, Inner/ultrastructure
- Lateral Line System/ultrastructure
- Metalloendopeptidases/genetics*
- Metalloendopeptidases/metabolism
- Microscopy, Electron, Scanning Transmission
- Mitochondria/metabolism*
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 33759764 Full text @ Elife
Citation
Alassaf, M., Halloran, M.C. (2021) Pregnancy associated plasma protein-aa regulates endoplasmic reticulum-mitochondria associations. eLIFE. 10:.
Abstract
Endoplasmic reticulum (ER) and mitochondria form close physical associations to facilitate calcium transfer, thereby regulating mitochondrial function. Neurons with high metabolic demands, such as sensory hair cells, are especially dependent on precisely regulated ER-mitochondria associations. We previously showed that the secreted metalloprotease Pregnancy associated plasma protein-aa (Pappaa) regulates mitochondrial function in zebrafish lateral line hair cells (Alassaf et al., 2019). Here, we show that pappaa mutant hair cells exhibit excessive and abnormally close ER-mitochondria associations, suggesting increased ER-mitochondria calcium transfer. pappaa mutant hair cells are more vulnerable to pharmacological induction of ER-calcium transfer. Additionally, pappaa mutant hair cells display ER stress and dysfunctional downstream processes of the ER-mitochondria axis including altered mitochondrial morphology and reduced autophagy. We further show that Pappaa influences ER-calcium transfer and autophagy via its ability to stimulate insulin-like growth factor-1 bioavailability. Together our results identify Pappaa as a novel regulator of the ER-mitochondria axis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping