Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes

摘要: NAD biosynthesis is of substantial interest because its important roles in regulating various biological processes. Nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3) considered a mitochondria-localized synthesis enzyme involved de novo and salvage pathways. Although the biochemical properties Nmnat3 are well documented, physiological function vivo remains unclear. In this study, we demonstrated that was localized cytoplasm mature erythrocytes critically regulated their pool. Deficiency mice caused splenomegaly hemolytic anemia, which associated with findings Nmnat3-deficient had markedly lower ATP levels shortened lifespans. However, level other tissues were not apparently affected by deficiency Nmnat3. LC-MS/MS-based metabolomics revealed glycolysis pathway blocked at glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step shortage coenzyme NAD. Stable isotope tracer analysis further resulted stall shift to pentose phosphate pathway. Our indicate critical maintenance pool impacts absence mice.