Major arc mitochondrial DNA deletions in cytochrome c oxidase-deficient human cochlear spiral ganglion cells.
CONCLUSIONS
This study suggests that cytochrome c oxidase subunit 3 (COX 3) expression is diminished in spiral ganglion cells from individuals with presbycusis. In addition to the mitochondrial DNA (mtDNA) common deletion (CD), other deletions involving the mtDNA major arc contribute to the observed deficit in COX 3 expression.


OBJECTIVE
To assess COX 3 deficiency in spiral ganglion cells from individuals with presbycusis and to determine whether deletions other than the CD contribute to this deficiency.


METHODS
COX 3 immunofluorescence staining of archival human temporal bone tissue sections from individuals with presbycusis and from age-matched normal-hearing individuals was performed and the intensity of spiral ganglion cell immunostaining was measured. Single COX 3-deficient spiral ganglion cells were isolated by laser microdissection (LMD) and the DNA was analyzed with duplex real-time PCR assays to assess the CD level and the total mtDNA major arc deletion level.


RESULTS
A statistically significant difference (p = 0.021) in the mean intensity of COX 3 immunofluorescence staining of spiral ganglion cells was observed between individuals with presbycusis and normal-hearing controls. The total mtDNA major arc deletion level was greater than the CD level in COX 3-deficient spiral ganglion cells.
Markaryan
Adam
A
Department of Surgery, University of Chicago, IL, USA.
Nelson
Erik G
EG
Hinojosa
Raul
R
D016022:Case-Control Studies; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006801:Humans; D042282:Microdissection; D008853:Microscopy; D016133:Polymerase Chain Reaction; D011304:Presbycusis / Q000235:genetics*; D017384:Sequence Deletion; D013136:Spiral Ganglion / Q000166:cytology*
D004272:DNA, Mitochondrial