Inherited pathogenic mitochondrial DNA mutations and gastrointestinal stem cell populations.

The Journal of Pathology
Tianhong SuLaura C Greaves

Abstract

Inherited mitochondrial DNA (mtDNA) mutations cause mitochondrial disease, but mtDNA mutations also occur somatically and accumulate during ageing. Studies have shown that the mutation load of some inherited mtDNA mutations decreases over time in blood, suggesting selection against the mutation. However, it is unknown whether such selection occurs in other mitotic tissues, and where it occurs within the tissue. Gastrointestinal epithelium is a canonical mitotic tissue rapidly renewed by stem cells. Intestinal crypts (epithelium) undergo monoclonal conversion with a single stem cell taking over the niche and producing progeny. We show: (1) that there is a significantly lower mtDNA mutation load in the mitotic epithelium of the gastrointestinal tract when compared to the smooth muscle in the same tissue in patients with the pathogenic m.3243A>G and m.8344A>G mutations; (2) that there is considerable variation seen in individual crypts, suggesting changes in the stem cell population; (3) that this lower mutation load is reflected in the absence of a defect in oxidative phosphorylation in the epithelium. This suggests that there is selection against inherited mtDNA mutations in the gastrointestinal stem cells that is in marked cont...Continue Reading

References

Nov 22, 2000·American Journal of Human Genetics·S RahmanA Suomalainen
Nov 5, 2003·The Journal of Clinical Investigation·Robert W TaylorDouglass M Turnbull
Apr 30, 2005·Nature Reviews. Genetics·Robert W Taylor, Doug M Turnbull
Feb 7, 2008·American Journal of Human Genetics·Harsha Karur RajasimhaDavid C Samuels
Jan 26, 2010·Experimental Gerontology·Laura C GreavesDoug M Turnbull
Sep 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Riikka H HämäläinenAnu Suomalainen
Feb 6, 2015·Annals of Neurology·Gráinne S GormanRobert McFarland
Sep 5, 2015·Neuropathology and Applied Neurobiology·Alexia ChrysostomouNichola Z Lax

❮ Previous
Next ❯

Citations

Feb 16, 2020·Journal of Molecular Evolution·David A LiberlesAndrew Storfer
Sep 25, 2018·The Journal of Pathology·Darryl Shibata
Jul 3, 2021·Life·Maria-Eleni Parakatselaki, Emmanuel D Ladoukakis

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay

Software Mentioned

PyroMark Assay design
ImageJ
PyroMark Q96

Related Concepts

Related Feeds

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.