Mitoferrin-1 is required for brain energy metabolism and hippocampus-dependent memory

Abstract Disturbed iron (Fe) ion homeostasis and mitochondrial dysfunction have been implicated in neurodegeneration. Both processes are related, because central Fe ion consuming biogenetic pathways take place in mitochondria and affect their oxidative energy metabolism. Iron is imported into mitochondria by the two homologous Fe ion importers mitoferrin-1 and mitoferrin-2. To elucidate more specifically the role of mitochondrial Fe ions for brain energy metabolism and for proper neuronal function, we generated mice with a neuron-specific knockout of mitoferrin-1 (Slc25a37−/− or mfrn-1−/−) and compared them with corresponding control littermates (mfrn-1flox/flox). Mice lacking neuronal mfrn-1 exhibited no obvious anatomical or behavioral abnormalities as neonates, young or adult animals. However, they exhibited a moderate decrease in brain mitochondrial O2-consumption with complex-I substrates of the electron transport chain (p