Tales from the crypt

Abstract

Intestinal colonic crypts are derived from a stem cell population located at the base of each crypt. A new analysis of mitochondrial function and of the rates of mitochondrial DNA (mtDNA) mutation in individual crypts shows that mtDNA mutations arise in stem cells - and at a surprisingly high frequency. Because crypts turn over extremely rapidly (about once per week), somatic mtDNA mutations can "take over the system" and even become homoplasmic, in a manner similar to what has been shown to occur in tumors.

Figure 1

(a) The respiratory chain. Nuclear DNA-encoded subunits are light gray; mtDNA-encoded subunits (see panel b) are dark gray. (b) Map of the human mitochondrial genome. Polypeptide-coding gene products (outside the circle) specify 7 subunits of NADH dehydrogenase-CoQ oxidoreductase (ND), 1 subunit of CoQ-cytochrome b oxidoreducase (Cyt b), 3 subunits of COX, and 2 subunits of ATP synthase (A). Protein synthesis gene products (inside the circle) specify 12S and 16S rRNAs, and 22 tRNAs (one-letter code). Figure modified from Schon and Manfredi (10).

Figure 2

Two-color histochemistry for SDH and COX reveals three types of crypts, with normal (a), deficient (b), and “mosaic” (c) patterns of mitochondrial function, reflecting the phenotype in the stem cells that gave rise to each type of crypt.