Quantum chemistry rules retinoid biology

This Perspective discusses how retinol catalyzes resonance energy transfer (RET) reactions pivotally important for mitochondrial energy homeostasis by protein kinase C δ (PKCδ). PKCδ signals to the pyruvate dehydrogenase complex, controlling oxidative phosphorylation. The PKCδ-retinol complex revers...

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Bibliographic Details
Published in:Communications biology 2023-02, Vol.6 (1), p.227-227, Article 227
Main Authors: Hammerling, Ulrich, Kim, Youn-Kyung, Quadro, Loredana
Format: Article
Language:English
Subjects:
631/443/319/333/1465
631/45/287
beta Carotene
Biology
Biomedical and Life Sciences
Cytochrome c
Electron transfer
Energy
Energy balance
Homeostasis
Kinases
Life Sciences
Mitochondria
Oxidative phosphorylation
Oxygenase
Perspective
Phosphorylation
Protein kinase C
Pyruvate dehydrogenase (lipoamide)
Pyruvic acid
Reactive oxygen species
Redox potential
Retinoids
Vitamin A
β-Carotene
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Summary:This Perspective discusses how retinol catalyzes resonance energy transfer (RET) reactions pivotally important for mitochondrial energy homeostasis by protein kinase C δ (PKCδ). PKCδ signals to the pyruvate dehydrogenase complex, controlling oxidative phosphorylation. The PKCδ-retinol complex reversibly responds to the redox potential of cytochrome c, that changes with the electron transfer chain workload. In contrast, the natural retinoid anhydroretinol irreversibly activates PKCδ. Its elongated conjugated-double-bond system limits the energy quantum absorbed by RET. Consequently, while capable of triggering the exergonic activating pathway, anhydroretinol fails to activate the endergonic silencing path, trapping PKCδ in the ON position and causing harmful levels of reactive oxygen species. However, physiological retinol levels displace anhydroretinol, buffer cyotoxicity and potentially render anhydroretinol useful for rapid energy generation. Intriguingly, apocarotenoids, the primary products of the mitochondrial β-carotene,9'-10'-oxygenase, have all the anhydroretinol-like features, including modulation of energy homeostasis. We predict significant conceptual advances to stem from further understanding of the retinoid-catalyzed RET. This Perspective explores retinol’s resonance energy transfer (RET) capabilities for reversible activation of PKC delta, so pivotal for OXPHOS control, and illuminates novel aspects of retinoid biology.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-04602-x