PUBLICATION
Inactivation of 3-hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy
- Authors
- Davuluri, G., Song, P., Liu, Z., Wald, D., Sakaguchi, T.F., Green, M.R., Devireddy, L.
- ID
- ZDB-PUB-160302-7
- Date
- 2016
- Source
- Proceedings of the National Academy of Sciences of the United States of America 113(11): E1460-9 (Journal)
- Registered Authors
- Sakaguchi, Takuya, Song, Ping
- Keywords
- 2,5-DHBA, bdh2, erythroid maturation, mitophagy, retrograde signaling
- Datasets
- GEO:GSE76509, GEO:GSE76508
- MeSH Terms
-
- Animals
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Mitophagy/physiology*
- Embryo, Nonmammalian/cytology
- PubMed
- 26929344 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Mitochondria are the site of iron utilization, wherein imported iron is incorporated into heme or iron-sulfur clusters. Previously, we showed that a cytosolic siderophore, which resembles a bacterial siderophore, facilitates mitochondrial iron import in eukaryotes, including zebrafish. An evolutionarily conserved 3-hydroxy butyrate dehydrogenase, 3-hydroxy butyrate dehydrogenase 2 (Bdh2), catalyzes a rate-limiting step in the biogenesis of the eukaryotic siderophore. We found that inactivation of bdh2 in developing zebrafish embryo results in heme deficiency and delays erythroid maturation. The basis for this erythroid maturation defect is not known. Here we show that bdh2 inactivation results in mitochondrial dysfunction and triggers their degradation by mitophagy. Thus, mitochondria are prematurely lost in bdh2-inactivated erythrocytes. Interestingly, bdh2-inactivated erythroid cells also exhibit genomic alterations as indicated by transcriptome analysis. Reestablishment of bdh2 restores mitochondrial function, prevents premature mitochondrial degradation, promotes erythroid development, and reverses altered gene expression. Thus, mitochondrial communication with the nucleus is critical for erythroid development.
Genes / Markers
Figure Gallery (11 images)
/ 2
/ 2
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping