Evidence for compartmentalization of mammalian carotenoid metabolism

Article

关键词: BETA-CAROTENE;    RETINOIC ACID;    VITAMIN-A;    EXCENTRIC CLEAVAGE;    IN-VITRO;    MACULAR DEGENERATION;    ENZYMATIC CLEAVAGE;    ESCHERICHIA-COLI;    RAT-LIVER;    IDENTIFICATION;   

DOI  :  10.1096/fj.14-252411

来源: SCIE

【 摘 要 】

The critical role of retinoids (vitamin A and its derivatives) for vision, reproduction, and survival has been well established. Vitamin A is produced from dietary carotenoids such as beta-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related beta-carotene metabolizing enzyme, BCO2, has led to a prolonged debate about its relevance in vitamin A biology. While BCO1 cleaves provitamin A carotenoids, BCO2 is more promiscuous and also metabolizes non-provitamin A carotenoids such as zeaxanthin into long-chain apo-carotenoids. Herein we demonstrate, in cell lines, that human BCO2 is associated with the inner mitochondrial membrane. Different human BCO2 isoforms possess cleavable N-terminal leader sequences critical for mitochondrial import. Subfractionation of murine hepatic mitochondria confirmed the localization of BCO2 to the inner mitochondrial membrane. Studies in BCO2-knockout mice revealed that zeaxanthin accumulates in the inner mitochondrial membrane; in contrast, beta-carotene is retained predominantly in the cytoplasm. Thus, we provide evidence for a compartmentalization of carotenoid metabolism that prevents competition between BCO1 and BCO2 for the provitamin and the production of noncanonical beta-carotene metabolites.-Palczewski, G., Amengual, J., Hoppel, C. L., von Lintig, J. Evidence for compartmentalization of mammalian carotenoid metabolism.

【 授权许可】

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