Department of Food Science, Rutgers Center for Lipid Research and Institute of Food Nutrition and Health, Rutgers University, New Brunswick, NJ, USA.
Commun Biol. 2023 Feb 28;6(1):227. doi: 10.1038/s42003-023-04602-x.
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.
这篇观点文章讨论了视黄醇如何通过蛋白激酶 Cδ（PKCδ）催化共振能量转移（RET）反应，这些反应对于线粒体能量稳态至关重要。PKCδ 信号传递到丙酮酸脱氢酶复合物，控制氧化磷酸化。PKCδ-视黄醇复合物可逆地响应细胞色素 c 的氧化还原电位，而细胞色素 c 的氧化还原电位随着电子传递链工作量的变化而变化。相比之下，天然视黄醇脱水视黄醇不可逆地激活 PKCδ。其延长的共轭双键系统限制了通过 RET 吸收的能量量子。因此，虽然能够触发放能激活途径，但脱水视黄醇无法激活吸能沉默途径，使 PKCδ 被困在 ON 位置，并导致有害水平的活性氧。然而，生理视黄醇水平取代脱水视黄醇，缓冲细胞毒性，并可能使脱水视黄醇在快速能量产生方面有用。有趣的是，脱辅基类胡萝卜素，即线粒体 β-胡萝卜素 9'-10'-加氧酶的主要产物，具有所有脱水视黄醇样的特征，包括对能量稳态的调节。我们预测，对视黄醇催化的 RET 的进一步理解将带来重大的概念性进展。
