Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma

Yakob Yusnita, Md Desa Norsiah, A. Rahman A. Jamal

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mitochondrial Subunit ND1 (mtND1) gene is involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). Alteration of the electron transport components by mutations in mtDNA may compromise the normal electron flow. This could lead to an increase of bifurcation and generation of superoxidase radicals and increase oxidative stress in various types of cancer cells. Genomic DNA was extracted from thirty matched primary colorectal tumour tissues and matching non-tumour tissues. Blood samples were obtained from twenty-fi ve normal people. The mtNDI coding region was amplifi ed by step-down PCR. The purifi ed products were then subjected to direct sequencing and subsequently, the DNA sequences obtained were compared with the revised Cambridge Reference Sequence (rCRS) and MITOMAP. From the analysis, the mtND1 gene showed 11 (45.8%) different mutations and also 13 (54.2%) polymorphisms. The heteroplasmic mutation A4123A/G (I273I/V) might have a pathogenic signifi cance as it fulfi lls various pathogenic criteria. Three mutations, T3394C (Y30H), A3434G (Y43C) and C3497T (A64V) which occur in a highly conserved region were likely to alter the structure and function of the ND1 protein. We suggest that these mutations, and in combination with the polymorphic variance in mtDNA, may cause slight changes that generate subtly higher levels of toxic reactive oxygen species (ROS).

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalMalaysian Journal of Pathology
Volume32
Issue number2
Publication statusPublished - Dec 2010

Fingerprint

NADH Dehydrogenase
Colorectal Neoplasms
Mutation
Genes
Electron Transport
Mitochondrial DNA
Poisons
Oxidative Phosphorylation
Reactive Oxygen Species
Oxidative Stress
Electrons
Polymerase Chain Reaction
DNA
Neoplasms
Proteins

Keywords

  • Colorectal carcinoma
  • Mitochondrial DNA mutations
  • mtND1 gene
  • OXPHOS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

Cite this

Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma. / Yusnita, Yakob; Norsiah, Md Desa; A. Jamal, A. Rahman.

In: Malaysian Journal of Pathology, Vol. 32, No. 2, 12.2010, p. 103-110.

Research output: Contribution to journalArticle

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