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        In Situ PCR of the Common Human mtDNA Deletion: Is It Related to Apoptosis

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        We have developed an in situ polymerase chain reaction (PCR) assay for the elucidation of the human mitochondrial DNA4977 deletion (common mtDNA deletion), which occurs between two 13-bp direct repeats situated 4977 bp apart (1 ). Although the origin of the common mtDNA deletion is unknown, its presence in a muscle sample is associated with reduced energy capacity (2 ). My colleagues and I have demonstrated in age-matched putamen and frontal gyrus of the brain that levels of the common mtDNA deletion are statistically related to medical conditions associated with chronic hypoxia (3 ). No other factors we considered (age, sex, ethnicity, drug use, postmortem interval [PMI]) carried any statistical significance. This analysis strongly suggests that aging is not a factor (a factor investigated in many other studies with smaller sample sizes, see two paragraphs below, also refs. 4 and 5 ), inferring that there could be genetic regulation of the common mtDNA deletion. Likewise, it has been reported that the common mtDNA deletion levels induced by γ-radiation are directly related to radiosensitivity of the cells (6 ), again implicating regulation. Of note, a nuclear-encoded protein, a mitochondrial helicase, has recently been associated with multiple mtDNA deletions. However, it is apparently not associated with the common mtDNA deletion (7 ).
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