PUBLICATION
Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function
- Authors
- Alassaf, M., Daykin, E.C., Mathiaparanam, J., Wolman, M.A.
- ID
- ZDB-PUB-190618-2
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Wolman, Marc
- Keywords
- cell biology, neuroscience, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Calcium/metabolism*
- Cell Survival/genetics
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Hair Cells, Auditory/cytology
- Hair Cells, Auditory/metabolism*
- Humans
- Larva/genetics
- Larva/metabolism
- Metalloendopeptidases/genetics
- Metalloendopeptidases/metabolism
- Microscopy, Confocal
- Mitochondria/genetics
- Mitochondria/metabolism*
- Mutation
- Pregnancy-Associated Plasma Protein-A/genetics
- Pregnancy-Associated Plasma Protein-A/metabolism*
- Reactive Oxygen Species/metabolism*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 31205004 Full text @ Elife
Citation
Alassaf, M., Daykin, E.C., Mathiaparanam, J., Wolman, M.A. (2019) Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function. eLIFE. 8:.
Abstract
To support cell survival, mitochondria must balance energy production with oxidative stress. Inner ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. We identified a novel molecular regulator of the hair cells' mitochondria and survival: Pregnancy-associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants' enhanced hair cell loss can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator of hair cell survival and essential mitochondrial function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping