The human mitochondrial enzyme BCO2 exhibits catalytic activity toward carotenoids and apocarotenoids

Thomas, Linda D.; Bandara, Sepalika; Parmar, Vipulkumar M.; Ramkumar, Srinivasagan; Khadka, Nimesh; Golczak, Marcin; Kiser, Philip D.; Lintig, Johannes von

doi:10.1074/jbc.ra120.015515

Cited by 29 publications

(36 citation statements)

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“…We discovered that in the presence of the mBCO2 substrate β-carotene mBCO2 loses palmitoylation [ 34 ]. Knowing that BCO2 cleaves xanthophylls [ 17 , 48 , 49 ] we decided to run palmitoylation assays to study the palmitoylation status of mBCO2 in the presence of xanthophylls. We first tried to deliver xanthophylls with the detergent Tween 40 [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

“…The catalytic activity of mBCO2 towards certain oxidative metabolites of zeaxanthin was recently documented [ 17 ]. There are numerous other xanthophylls in the human diet.…”

Section: Discussionmentioning

confidence: 99%

“…Xanthophyll-binding proteins have been described for both zeaxanthin and lutein [ 16 ]. However, the role of β-carotene oxygenase 2 (BCO2), an enzyme that can cleave xanthophylls [ 17 ], is not thoroughly studied.…”

Section: Introductionmentioning

confidence: 99%

“…We chose to express mBCO2 in human cell culture because it has only one major isoform while human and monkey BCO2 have several major isoforms. Only one of these has a N-terminal mitochondrial signal and it is still hotly debated if this isoform manifests as an active BCO2 enzyme [ 17 , 29 , 30 , 31 ]. Here, using LUVs, we describe that lutein modulates the palmitoylation status of mouse BCO2 (mBCO2) and changes its cellular localization in HEK293F cells from mitochondria to nucleus upon binding.…”

Section: Introductionmentioning

confidence: 99%

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Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2

et al. 2021

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An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of β-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer’s disease symptoms. Mammalian β-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as β-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with β-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation.

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Section: Resultsmentioning

confidence: 99%

“…The catalytic activity of mBCO2 towards certain oxidative metabolites of zeaxanthin was recently documented [ 17 ]. There are numerous other xanthophylls in the human diet.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2

et al. 2021

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“…Vitamin A deficiency is associated with age-related macular degeneration. BCO2 was just demonstrated to exhibit catalytic activity towards carotenoids and apocarotenoids [ 137 ].…”

Section: At Work In the Bone Marrow For Hematopoiesis And Maintenamentioning

confidence: 99%

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina

Bandara

Lintig

2022

BioEssays

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Carotenoids play pivotal roles in vision as light filters and precursor of chromophore.Many vertebrates also display the colorful pigments as ornaments in bare skin parts and feathers. Proteins involved in the transport and metabolism of these lipids have been identified including class B scavenger receptors and carotenoid cleavage dioxygenases. Recent research implicates members of the Aster protein family, also known as GRAM domain-containing (GRAMD), in carotenoid metabolism. These multi-domain proteins facilitate the intracellular movement of carotenoids from their site of cellular uptake by scavenger receptors to the site of their metabolic processing by carotenoid cleavage dioxygenases. We provide a model how the coordinated interplay of these proteins and their differential expression establishes carotenoid distribution patterns and function in tissues, with particular emphasis on the human retina.

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The human mitochondrial enzyme BCO2 exhibits catalytic activity toward carotenoids and apocarotenoids

Cited by 29 publications

References 66 publications

Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2

Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina

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