Retinol as electron carrier in redox signaling, a new frontier in vitamin A research

Nature uses carotenoids and retinoids as chromophores for diverse energy conversion processes. The key structural feature enabling the interaction with light and other manifestations of electro-magnetism is the conjugated double-bond system that all members of this superfamily share in common. Among retinoids, retinaldehyde alone was long known as the active chromophore of vision in vertebrates and invertebrates, as well of various light-driven proton and ion pumps in Archaea. Until now, vitamin A (retinol) was solely regarded as a biochemical precursor for bioactive retinoids such as retinaldehyde and retinoic acid (RA), but recent results indicate that this compound has its own physiology. It functions as an electron carrier in mitochondria. By electronically coupling protein kinase Cδ (PCKδ) with cytochrome c, vitamin A enables the redox activation of this enzyme. This review focuses on the biochemistry and biology of the PCKδ signaling system, comprising PKCδ, the adapter protein p66Shc, cytochrome c and retinol. This complex positively regulates the conversion of pyruvate to acetyl-coenzyme A (CoA) by the pyruvate dehydrogenase enzyme. Vitamin A therefore plays a key role in glycolytic energy generation. The emerging paradigm of retinol as electron-transfer agent is potentially transformative, opening new frontiers in retinoid research.