PUBLICATION
BCDO2 acts as a carotenoid scavenger and gatekeeper for the mitochondrial apoptotic pathway
- Authors
- Lobo, G.P., Isken, A., Hoff, S., Babino, D., and von Lintig, J.
- ID
- ZDB-PUB-120706-25
- Date
- 2012
- Source
- Development (Cambridge, England) 139(16): 2966-2977 (Journal)
- Registered Authors
- Lobo, Glenn
- Keywords
- none
- MeSH Terms
-
- Mitochondria/metabolism*
- Fenretinide/pharmacology
- Models, Biological
- Cell Line
- Erythropoiesis/genetics
- Erythropoiesis/physiology
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism
- Dioxygenases
- Humans
- Gene Expression Regulation, Enzymologic
- Oxidative Stress
- Base Sequence
- Fatty Acid Desaturases/genetics
- Fatty Acid Desaturases/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Gene Expression Regulation, Developmental
- RNA, Small Interfering/genetics
- Apoptosis/drug effects
- Apoptosis/physiology*
- Animals
- Carotenoids/metabolism*
- Carotenoids/pharmacology
- Anemia/enzymology
- Anemia/genetics
- Acetylcysteine/pharmacology
- Gene Knockdown Techniques
- Oxygenases/antagonists & inhibitors
- Oxygenases/genetics
- Oxygenases/metabolism*
- PubMed
- 22764054 Full text @ Development
Citation
Lobo, G.P., Isken, A., Hoff, S., Babino, D., and von Lintig, J. (2012) BCDO2 acts as a carotenoid scavenger and gatekeeper for the mitochondrial apoptotic pathway. Development (Cambridge, England). 139(16):2966-2977.
Abstract
Carotenoids and their metabolites are widespread and exert key biological functions in living organisms. In vertebrates, the carotenoid oxygenase BCMO1 converts carotenoids such as β,β-carotene to retinoids, which are required for embryonic pattern formation and cell differentiation. Vertebrate genomes encode a structurally related protein named BCDO2 but its physiological function remains undefined. Here, we show that BCDO2 is expressed as an oxidative stress-regulated protein during zebrafish development. Targeted knockdown of this mitochondrial enzyme resulted in anemia at larval stages. Marker gene analysis and staining for hemoglobin revealed that erythropoiesis was not impaired but that erythrocytes underwent apoptosis in BCDO2-deficient larvae. To define the mechanism of this defect, we have analyzed the role of BCDO2 in human cell lines. We found that carotenoids caused oxidative stress in mitochondria that eventually led to cytochrome c release, proteolytic activation of caspase 3 and PARP1, and execution of the apoptotic pathway. Moreover, BCDO2 prevented this induction of the apoptotic pathway by carotenoids. Thus, our study identifying BCDO2 as a crucial protective component against oxidative stress establishes this enzyme as mitochondrial carotenoid scavenger and a gatekeeper of the intrinsic apoptotic pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping