Functional Impact Of ?, ?-carotene-9�, 10�-oxygenase 2 (Bco2) in Hepatic Mitochondria

Abstract

?, ?-carotene-9�, 10�-dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme in the inner membrane of mitochondria. However, BCO2 is inactivated in human macula where xanthophyll is preferentially accumulated. The purpose of this study is to determine whether intact BCO2 protein impacts integrity of hepatic mitochondrial function in mice. Male BCO2 knockout (KO) and the genetic background wild type (WT) mice, at 6 weeks of age, were used. Isolated hepatic mitochondria were subjected to mitochondrial proteome profiling (by LC-MS/MS) and functional integrity assay (by the assay of coupling and electron flow). Liver tissue metabolomics was also explored. The basal respiratory rate, the proton leak and the maximal ATP production were all significantly elevated in the BCO2 knockout liver compared to wild type liver. The capacities of mitochondrial complex II and complex IV was greater in knockout mice than that in the wild type mice. Mitochondrial proteomic profiling results indicated alterations of enzymes and proteins involved in fatty acid ?�oxidation, the tricarboxylic acid cycle, ETC/oxidative phosphorylation, and the metabolism of carotenoids. The global metabolic profiles showed that increased level of oxidative stress and alterations of lipid metabolism in BCO2 knockout liver compared to wild type liver. In conclusion, BCO2 is essential to maintain the hepatic mitochondrial normal function.