| First Author | Diaz F | Year | 2008 |
| Journal | Gut | Volume | 57 |
| Issue | 2 | Pages | 232-42 |
| PubMed ID | 17951359 | Mgi Jnum | J:294601 |
| Mgi Id | MGI:6451277 | Doi | 10.1136/gut.2006.119180 |
| Citation | Diaz F, et al. (2008) Pathophysiology and fate of hepatocytes in a mouse model of mitochondrial hepatopathies. Gut 57(2):232-42 |
| abstractText | BACKGROUND: Although oxidative phosphorylation defects can affect the liver, these conditions are poorly understood, partially because of the lack of animal models. AIMS: To create and characterise the pathophysiology of mitochondrial hepatopathies in a mouse model. METHODS: A mouse model of mitochondrial hepatopathies was created by the conditional liver knockout (KO) of the COX10 gene, which is required for cytochrome c oxidase (COX) function. The onset and progression of biochemical, molecular and clinical phenotypes were analysed in several groups of animals, mostly at postnatal days 23, 56, 78 and 155. RESULTS: Biochemical and histochemical analysis of liver samples from 23-56-day-old KO mice showed liver dysfunction, a severe COX deficiency, marked mitochondrial proliferation and lipid accumulation. Despite these defects, the COX-deficient hepatocytes were not immediately eliminated, and apoptosis followed by liver regeneration could be observed only at age 78 days. Hepatocytes from 56-78-day-old KO mice survived despite very low COX activity but showed a progressive depletion of glycogen stores. In most animals, hepatocytes that escaped COX10 ablation were able to proliferate and completely regenerate the liver between days 78 and 155. CONCLUSIONS: The results showed that when faced with a severe oxidative phosphorylation defect, hepatocytes in vivo can rely on glycolysis/glycogenolysis for their bioenergetic needs for relatively long periods. Ultimately, defective hepatocytes undergo apoptosis and are replaced by COX-positive cells first observed in the perivascular regions. |
