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Evidence for compartmentalization of mammalian carotenoid metabolism.

ABSTRACT: 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 ?-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related ?-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 nonprovitamin 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, ?-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 ?-carotene metabolites.

SUBMITTER: Palczewski G

PROVIDER: S-EPMC4202098 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Evidence for compartmentalization of mammalian carotenoid metabolism.

Palczewski Grzegorz G Amengual Jaume J Hoppel Charles L CL von Lintig Johannes J

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20140707 10

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 β-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related β-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 al ...[more]

PMID: 25002123

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Evidence for compartmentalization of mammalian carotenoid metabolism.

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Evidence for compartmentalization of mammalian carotenoid metabolism.

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