BCDO2 acts as a carotenoid scavenger and gatekeeper for the mitochondrial apoptotic pathway
| Autor: | Sylvia Hoff, Andrea Isken, Johannes von Lintig, Darwin Babino, Glenn P. Lobo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Fatty Acid Desaturases
Fenretinide Cellular differentiation Caspase 3 Apoptosis Oxidative phosphorylation Mitochondrion Biology Models Biological Gene Expression Regulation Enzymologic Cell Line Dioxygenases Animals Humans Erythropoiesis RNA Small Interfering Molecular Biology Carotenoid Zebrafish Research Articles chemistry.chemical_classification Base Sequence Cytochrome c Carotenoid oxygenase Gene Expression Regulation Developmental Anemia Zebrafish Proteins Carotenoids Acetylcysteine Mitochondria Oxidative Stress Biochemistry chemistry Gene Knockdown Techniques biology.protein Oxygenases Developmental Biology |
| Zdroj: | Development (Cambridge, England). 139(16) |
| ISSN: | 1477-9129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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