The mitochondrial PKCδ/retinol signal complex exerts real-time control on energy homeostasis

Publication date: Available online 10 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Youn-Kyung Kim, Ulrich HammerlingAbstractThe review focuses on the role of vitamin A (retinol) in the control of energy homeostasis, and on the manner in which certain retinoids subvert this process, leading potentially to disease. In eukaryotic cells, the pyruvate dehydrogenase complex (PDHC) is negatively regulated by four pyruvate dehydrogenase kinases (PDKs) and two antagonistically acting pyruvate dehydrogenase phosphatases (PDPs). The second isoform, PDK2, is regulated by an autonomous mitochondrial signal cascade that is anchored on protein kinase Cδ (PKCδ), where retinoids play an indispensible co-factor role. Along with its companion proteins p66Shc, cytochrome c, and vitamin A, the PKCδ/retinol complex is located in the intermembrane space of mitochondria. At this site, and in contrast to cytosolic locations, PKCδ is activated by the site-specific oxidation of its cysteine-rich activation domain (CRD) that is configured into a complex RING-finger. Oxidation involves the transfer of electrons from cysteine moieties to oxidized cytochrome c, a step catalyzed by vitamin A. The PKCδ/retinol signalosome monitors the internal cytochrome c redox state that reflects the workload of the respiratory chain. Upon sensing demands for energy PKCδ signals the PDHC to increase glucose-derived fuel flux entering the KREBS cycle. Convers...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research