Nutrient-gene interactions: dietary vitamin A and mitochondrial gene expression.

The BHE/Cdb rat is a model for mitochondrial diabetes due to a mutation in the ATPase 6 gene. These rats require more dietary vitamin A to optimize mitochondrial function than do normal Sprague-Dawley rats. To determine a possible mechanism for this effect, cultured hepatocytes and hepatic tissues were studied. ATPase 6 (F0ATPase subunit a), retinoic acid receptors (RARs), and mitochondrial transcription factor A (mtTFA) gene products were determined using Western blot analysis. Northern analysis was used to determine ATPase 6, ATPase 6,8, and ND1 mRNA. Mitochondrial density was determined using confocal microscopy. Dose response studies using primary hepatocyte cultures showed that both ATPase 6 gene product and mRNA were optimized with additions of 10(-9) M retinoic acid. Retinoic acid receptors were found in the mitochondrial compartment. MtTFA levels were increased by vitamin A. Mitochondrial density was greater in the BHE/Cdb tissue than in Sprague-Dawley tissue. These results show that vitamin A affects mitochondrial function via an effect on both nuclear and mitochondrial encoded genes.