Impact of a novel homozygous mutation in nicotinamide nucleotide transhydrogenase on mitochondrial DNA integrity in a case of familial glucocorticoid deficiency

Conclusions Our results indicated that (i) mitochondrial biogenesis (citrate synthase activity) and/or mtDNA replication (mtDNA copy number) were affected at ≤60% NNT activity because these parameters were affected in individuals carrying either one or both mutated alleles; and (ii) other outcomes (mtDNA deletions, protein tyrosine nitration, OXPHOS capacity) were affected at ≤30% NNT activity as also observed in murine cerebellar mitochondria from C57BL/6J (NNT -/-) vs. C57BL/6JN (NNT +/+) substrains. General significance By studying a family affected with a novel point mutation in the NNT gene, a gene-dose response was found for various mitochondrial outcomes providing for novel insights into the role of NNT in the maintenance of mtDNA integrity beyond that described for preventing oxidative stress.
Source: BBA Clinical - Category: Biochemistry Source Type: research