Hiding in plain sight: Uncovering a new function of vitamin A in redox signaling

• Published in: Biochimica et biophysica acta 2012-01, Vol.1821 (1), p.241-247
• Main Authors: Hoyos, Beatrice, Acin-Perez, Rebeca, Fischman, Donald A., Manfredi, Giovanni, Hammerling, Ulrich
• Format: Article
• Language: English
• Subjects: Acetyl Coenzyme A - metabolism; Animals; Citric Acid Cycle - physiology; Cytochromes c - metabolism; Electron Transport - physiology; Energy homeostasis; Humans; Mitochondria - metabolism; Mitochondrion; Oxidation-Reduction; Oxidative Phosphorylation; Protein Kinase C-delta - metabolism; Protein kinase Cδ; Pyruvate Dehydrogenase Complex - metabolism; Signal Transduction; Vitamin A; Vitamin A - analogs & derivatives; Vitamin A - metabolism
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2011.06.014

The protein kinase Cδ signalosome modulates the generation of acetyl-Coenzyme A from glycolytic sources. This module is composed of four interlinked components: PKCδ, the signal adapter p66Shc, cytochrome c, and vitamin A. It resides in the intermembrane space of mitochondria, and is at the center of a feedback loop that senses upstream the redox balance between oxidized and reduced cytochrome c as a measure of the workload of the respiratory chain, and transmits a forward signal to the pyruvate dehydrogenase complex to adjust the flux of fuel entering the tricarboxylic acid cycle. The novel role of vitamin A as co-activator and potential electron carrier, required for redox activation of PKCδ, is discussed. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. ► PKCδ, p66Shc, cytochrome C and vitamin A form a mitochondrial signal module. ► The PKCδ signalosome senses and adjusts the workload of the respiratory chain. ► The PKCδ signalosome signals the pyruvate dehydrogenase complex to adjust fuel flux. ► Vitamin A serves as co-factor and electron carrier for redox activation of PKCδ.