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Davuluri 2016 Proc Natl Acad Sci U S A

From Bioblast
Publications in the MiPMap
Davuluri G, Song P, Liu Z, Wald D, Sakaguchi TF, Green MR, Devireddy L (2016) Inactivation of 3-hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy. Proc Natl Acad Sci U S A 113:E1460-9.

Β» PMID: 26929344 Open Access

Davuluri G, Song P, Liu Z, Wald D, Sakaguchi TF, Green MR, Devireddy L (2016) Proc Natl Acad Sci U S A

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. β€’ Keywords: 2, 5-DHBA, bdh2, Erythroid maturation, Mitophagy, Retrograde signaling


Labels: MiParea: Respiration, Genetic knockout;overexpression, Developmental biology 


Organism: Zebrafish  Tissue;cell: Blood cells  Preparation: Intact cells 


Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k 

2016-09