Disease relevance of MT-ND4L

• An example of Leber hereditary optic neuropathy not involving a mutation in the mitochondrial ND4 gene [1].
• It is shown here, however, that neither this biochemical lesion nor the optic neuropathy are due to the mutation at nucleotide position 11,778 of the mitochondrial ND4 gene first identified by Wallace et al. in several LHON pedigrees [1].

High impact information on MT-ND4L

• Within its 17.8 x 10(3) base-pair insert a 1.6 x 10(3) base-pair mtDNA fragment was similar to three non-sequential coding genes of human mtDNA, including a part of the 12 S ribosomal RNA (684-971), the cytochrome oxidase I (6553-7302), and two NADH dehydrogenase [ND4L/ND4] (10,606-11,159) [2].
• In addition, a synonymous SNP in the codon 76 of the MTND4L gene was found in the single haplotype III animal [3].
• We report here the characterization of a new primary LHON mutation in the mtDNA ND4L gene at nucleotide pair 10663 [4].
• The ND4L gene (interrupted by one intervening sequence) potentially encodes an 89 residue long hydrophobic protein that shares about 26% homology (or 41% homology if conservative amino acid substitutions are allowed) with the analogous human mitochondrial protein [5].
• Mainly the ND4-ND4L region was affected, as evidenced by the PCR; however, other regions of the mitochondrial genome also showed deletions of varying size and extent, suggesting multiple deletions of the mitochondrial DNA [6].

Biological context of MT-ND4L

• RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively [7].

Anatomical context of MT-ND4L

• In particular, almost all nuclear (except MLRQ) and 5 mitochondria DNA encoded subunits (except ND4L and ND6) were identified [8].

Other interactions of MT-ND4L

• Starting from a cohort of 50 NADH-oxidoreductase (complex I) deficient patients, we carried out the systematic sequence analysis of all mitochondrially encoded complex I subunits (ND1 to ND6 and ND4L) in affected tissues [9].
• In one patient, only genes of ND5, ND4L as well as tRNA(Leu(CUN)), tRNA(Ser(AGY)), and tRNA(His) were deleted [10].

References