Essential role of mitochondria in pyrimidine metabolism

Abstract

Mitochondrial enzymes contribute to several discrete areas of metabolism in the cell. In particular, a member of the electron transport chain, dihydroorotate dehydrogenase (DHODH), in the inner mitochondrial membrane, contributes to compartmentation and metabolic channelling in the cytosolic enzymes, clustered around the mitochondria, which catalyse de novo synthesis of UMP. It is clear that the cytosolic pyrimidine pools must respond to demand for membrane synthesis, RNA synthesis and DNA replication as a prerequisite for the proliferation of normal and malignant cells. Mitochondria are also important in the salvage of nucleosides and deoxynucleosides, whose interconversion and catabolism are crucial to maintenance of mitochondrial DNA. A new theme emerges from recent research on the deoxynucleotide pools in mitochondria. In turn, the integrity of mtDNA is essential for that of the genome.