1. Age-associated mitochondrial complex I deficiency is linked to increased stem cell proliferation rates in the mouse colon.
- Author
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Stamp C, Whitehall JC, Smith ALM, Houghton D, Bradshaw C, Stoll EA, Blain AP, Turnbull DM, and Greaves LC
- Subjects
- Animals, Cell Proliferation, Female, Mice, Inbred C57BL, Mitochondria metabolism, Oxidative Phosphorylation, Thymidine metabolism, Mice, Aging pathology, Colon pathology, Electron Transport Complex I deficiency, Mitochondrial Diseases pathology, Stem Cells pathology
- Abstract
One of the hallmarks of aging is an accumulation of cells with defects in oxidative phosphorylation (OXPHOS) due to mutations of mitochondrial DNA (mtDNA). Rapidly dividing tissues maintained by stem cells, such as the colonic epithelium, are particularly susceptible to accumulation of OXPHOS defects over time; however, the effects on the stem cells are unknown. We have crossed a mouse model in which intestinal stem cells are labelled with EGFP (Lgr5-EGFP-IRES-creERT2) with a model of accelerated mtDNA mutagenesis (PolgA
mut/mut ) to investigate the effect of OXPHOS dysfunction on colonic stem cell proliferation. We show that a reduction in complex I protein levels is associated with an increased rate of stem cell cycle re-entry. These changes in stem cell homeostasis could have significant implications for age-associated intestinal pathogenesis., (© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)- Published
- 2021
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