ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
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- Altered lactate/pyruvate ratio may be responsible for aging-associated intestinal barrier dysfunction in male rats.Biogerontology · 2024Article
- Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate.Cellular and molecular life sciences : CMLS · 2024Review
- Mitochondrial DNA mutations in ageing and cancer.Molecular oncology · 2022Review
- Phase II Feasibility Study of the Efficacy, Tolerability, and Impact on the Gut Microbiome of a Low-Residue (Fiber) Diet in Adult Patients With Mitochondrial Disease.Gastro hep advances · 2022Article
- Progressive alterations in amino acid and lipid metabolism correlate with peripheral neuropathy inScience advances · 2021Article
- Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate.Cell stem cell · 2021Review
- Age-associated mitochondrial complex I deficiency is linked to increased stem cell proliferation rates in the mouse colon.Aging cell · 2021Article
- Age-induced mitochondrial DNA point mutations are inadequate to alter metabolic homeostasis in response to nutrient challenge.Aging cell · 2020Article
- Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis.Nature cancer · 2020Article
- The rise and rise of mitochondrial DNA mutations.Open biology · 2020Review
- DNA damage in aging, the stem cell perspective.Human genetics · 2020Review
- Age-Related Deterioration of Mitochondrial Function in the Intestine.Oxidative medicine and cellular longevity · 2020Review
- Voluntary exercise normalizes the proteomic landscape in muscle and brain and improves the phenotype of progeroid mice.Aging cell · 2019Article
- LncRNAs regulating stemness in aging.Aging cell · 2019Review
- Mitochondria as central regulators of neural stem cell fate and cognitive function.Nature reviews. Neuroscience · 2019Review
- Mito-mice∆ and mitochondrial DNA mutator mice as models of human osteoporosis caused not by aging but by hyperparathyroidism.Experimental animals · 2018Article
- Mutations of mitochondrial DNA are not major contributors to aging of fruit flies.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Impact of Age-Related Mitochondrial Dysfunction and Exercise on Intestinal Microbiota Composition.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
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Abstract
Changes in intestinal absorption of nutrients are important aspects of the aging process. To address this issue, we investigated the impact of accelerated mitochondrial DNA mutations on the stem/progenitor cells in the crypts of Lieberkühn in mice homozygous for a mitochondrial DNA polymerase gamma mutation, Polg(D257A), that exhibit accelerated aging phenotype. As early as 3-7 mo of age, the small intestine was significantly enlarged in the PolgD257A mice. The crypts of the PolgD257A mice contained 20% more cells than those of their wild-type littermates and exhibited a 10-fold increase in cellular apoptosis primarily in the stem/progenitor cell zones. Actively dividing cells were proportionally increased, yet a significantly smaller proportion of cells was in the S phase of the cell cycle. Stem cell-derived organoids from PolgD257A mice failed to develop fully in culture and exhibited fewer crypt units, indicating an impact of the mutation on the intestinal epithelial stem/progenitor cell maintenance. In addition, epithelial cell migration along the crypt-villus axis was slowed and less organized, and the ATP content in the villi was significantly reduced. On a high-fat, high-carbohydrate diet, PolgD257A mice showed significantly restricted absorption of excess lipids accompanied by an increase in fecal steatocrits. We conclude that the PolgD257A mutation causes cell cycle dysregulation in the crypts leading to the age-associated changes in the morphology of the small intestine and contributes to the restricted absorption of dietary lipids.
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