Mutation in mitochondrial complex I ND6 subunit is associated with defective response to hypoxia in human glioma cells

Molecular Cancer
Carrie DeHaanJoan Allalunis-Turner

Abstract

Hypoxia-tolerant human glioma cells reduce oxygen consumption rate in response to oxygen deficit, a defense mechanism that contributes to survival under moderately hypoxic conditions. In contrast, hypoxia-sensitive cells lack this ability. As it has been previously shown that hypoxia-tolerant (M006x, M006xLo, M059K) and -sensitive (M010b) glioma cells express differences in mitochondrial function, we investigated whether mitochondrial DNA-encoded mutations are associated with differences in the initial response to oxygen deficit. The mitochondrial genome was sequenced and 23 mtDNA alterations were identified, one of which was an unreported mutation (T-C transition in base pair 14634) in the hypoxia-sensitive cell line, M010b, that resulted in a single amino acid change in the gene encoding the ND6 subunit of NADH:ubiquinone oxidoreductase (Complex I). The T14634C mutation did not abrogate ND6 protein expression, however, M010b cells were more resistant to rotenone, an agent used to screen for Complex I mutations, and adriamycin, an agent activated by redox cycling. The specific function of mtDNA-encoded, membrane-embedded Complex I ND subunits is not known at present. Current models suggest that the transmembrane arm of Complex...Continue Reading

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Datasets Mentioned

BETA
GM38

Methods Mentioned

BETA
PCR
xenograft
flow cytometry

Software Mentioned

MITOMAP
Perl
Swiss
MODELLER
ImageQuant
BLAST
_ OPTIMIZER
Prism GraphPad
CLUSTAL W
PSI

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