Disease relevance of MT-ND5

• The upregulation of ND5 was not observed when Int407 was infected with Escherichia coli strains [1].
• Mitochondrial ND5 mutations in idiopathic Parkinson's disease [2].
• In the third AD+PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber's hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene [3].
• Atypical Leigh syndrome associated with the D393N mutation in the mitochondrial ND5 subunit [4].
• Upregulation of human mitochondrial NADH dehydrogenase subunit 5 in intestinal epithelial cells is modulated by Vibrio cholerae pathogenesis [1].

High impact information on MT-ND5

• In 70% of the mtDNA of this Pearson cell line a deletion from within the COX II gene to within the ND5 gene was present [5].
• The role of the ND5 gene in LHON: characterization of a new, heteroplasmic LHON mutation [6].
• Most such cases have been assumed to be caused by nuclear gene defects, but recently an increasing number have been shown to be caused by mutations in the mitochondrially encoded complex I subunit genes ND4, ND5, and ND6 [7].
• Two mitochondrial DNA mutations in complex I subunit genes, G14459A in ND6, and T12706C in ND5, have been associated with complex I deficiency and LD [8].
• Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS [9].

Biological context of MT-ND5

• In contrast, a remarkable upregulation of ND5 expression (200-fold) was observed in a hyperadherent icmF insertion mutant with reduced motility [1].
• Using RNA arbitrarily primed PCR, ND5 a mitochondria encoded subunit of complex I of the mitochondrial respiratory chain was found to be upregulated in the human intestinal epithelial cell line Int407 following exposure to V. cholerae [1].
• Infection of the monolayer with aflagellate non-motile mutant of V. cholerae O395 showed a very significant (59-fold) downregulation of ND5 [1].
• Thus, infection of Int407 with virulence mutant strains of V. cholerae revealed that the ND5 expression is modulated by the virulence of V. cholerae in a ToxT independent manner [1].
• We prospectively evaluated low frequency, amino acid changing, heteroplasmic mutations in a narrow region of ND5, a mitochondrial gene encoding a complex I subunit, in brain tissue from PD and controls [2].

Anatomical context of MT-ND5

• These results clearly indicate that both motility and adherence to intestinal epithelial cells are possible triggering factors contributing to ND5 mRNA expression by V. cholerae [1].
• Skeletal muscle mitochondrial DNA (mtDNA) analysis showed that all patients harbored a heteroplasmic G13513A mutation in the ND5 subunit gene [10].
• We report a novel G13513A mutation in the mitochondrial ND5 gene in a patient who had morphologically and biochemically abnormal muscle mitochondria and died at age 45 with a diagnosis of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) [11].
• Structure and expression of the overlapping ND4L and ND5 genes of Neurospora crassa mitochondria [12].

Associations of MT-ND5 with chemical compounds

• A second individual harbored a novel substitution of threonine with serine at position 536 of the ND5 protein [13].
• Consequently, there is a 30-35% reduction in the electron flow through Complex I compared with that through Complex II, and an increased lactate/pyruvate ratio, in the ND1 and ND4 mutants, but these factors were unaffected in the secondary ND5 mutants [14].
• In patient 2, a 9-bp directly repeated sequence of 5'-ACCTCCCTC-3' (where A = adenine, C = cytosine, and T = thymine) was found at the boundaries of a deleted segment spanning 7221 bp between the CO1 and ND5 genes [15].
• Two regions of the mtDNA of Atlantic herring (Clupea harengus), ND3/4 and ND5/6, were surveyed by RFLP analysis to assess the effects of marker variability on the power of statistical tests [16].
• We identified a heteroplasmic and a homoplasmic SNP at codon 507 in the subunit 5 (MTND5) of complex I. The heteroplasmic haplotype I-specific valine to methionine substitution represents a nonconservative amino acid change and was found in 11 myelopathic and eight non-myelopathic cheetahs with levels ranging from 29% to 79% [17].

Physical interactions of MT-ND5

• A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients [18].

Other interactions of MT-ND5

• Four replacement mutations restricted only to LHON families were found, one in the ND1 gene at nt 4025, and three in the ND5 gene at nt 12,811, 13,637, and 13,967 [19].
• One proband had a non-synonymous A14062G mutation in the ND5 gene and the other had a non-synonymous G15221A mutation in the cytochrome b gene and a T1391C mutation in the 12S ribosomal RNA gene, whose importance in disease expression remains to be clarified [20].
• Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations [9]?
• In one patient, only genes of ND5, ND4L as well as tRNA(Leu(CUN)), tRNA(Ser(AGY)), and tRNA(His) were deleted [21].
• Tissue specimens from four species of Neotropical small cats (Oncifelis geoffroyi, N = 38; O. guigna, N = 6; Leopardus tigrinus, N = 32; Lynchailurus colocolo, N = 22) collected from throughout their distribution were examined for patterns of DNA sequence variation using three mitochondrial genes, 16S rRNA, ATP8, and NADH-5 [22].

Analytical, diagnostic and therapeutic context of MT-ND5

• Sequence analysis of cardiac mtDNA revealed 4 patients harbouring heteroplasmic mtDNA mutations in cytb, tRNAArg, and ND5 at highly conserved positions [23].
• Antibodies raised against an internal peptide close to the N-terminus of the ND5 subunit and antibodies raised against an internal epitope of the ND6 subunit also reacted in both the immunoblotting and immunoprecipitation assays [24].
• Genealogical trees have been constructed using mitochondrial ND5 gene sequences of 78 Damaster (s. str.) specimens from all over the Japanese Islands. Eight lineages (called races in this paper) have been recognized [25].

References