ng, reported by Douglass Turnbull and colleagues from the University of Newcastle upon Tyne in the November 3 issue of the Journal of Clinical Investigation, could have profound implications for our understanding of the potential importance of these mutations in aging and cancer.

In addition to their role in tissue and organ formation during embryonic development, stem cells are also called upon to repopulate cells that undergo continual turnover. It stands to reason that if mtDNA is always replicating in cells, then somatic mtDNA mutations could also arise in stem cells. However, evidence to indicate that these mutations do indeed happen, and if so, at what rate, has been lacking.

Turnbull and colleagues provide evidence that at least one population of stem cells - those giving rise to intestinal colonic crypts do indeed harbor somatic mtDNA mutations, which, even more surprisingly, arise at a relatively high frequency. The colonic crypt provides an ideal system for study as crypt cells are all derived from one or two single cells stem cells located at the base of each crypt. Therefore any mtDNA mutation found in the crypt must have been amplified from that very mutation in the stem cell itself. Turnbull and colleagues used molecular, histological, and biochemical means to identify the mutation-carrying cells throughout the crypt. The authors determined that the rate of mtDNA mutation 5 x 10-5 per genome per day far exceeded that of nuclear DNA.

In an accompanying commentary in the same issue, Eric Schon from Columbia University in New York discusses how the use of colonic crypts as a stem cell model system should allow investigators to better study the dynamics underlying the shift from heteroplasmy (the coexistence, within the same cell, of both wild-type and mutated mtDNA) to homoplasmy (the presence of completely normal or completely mutant mtDNA) the latter of which has been shown to occur in tumors.

TITLE: Mito
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
3-Nov-2003

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