Abstract
Maternally inherited mitochondrial DNA (mtDNA) has been suggested to be a genetic factor for diabetes. Reports have shown a decrease of mtDNA content in tissues of diabetic patients. We investigated the effects of mtDNA depletion on glucose metabolism by use of rho(0) SK-Hep1 human hepatoma cells, whose mtDNA was depleted by long-term exposure to ethidium bromide. The rho(0) cells failed to hyperpolarize mitochondrial membrane potential in response to glucose stimulation. Intracellular ATP content, glucose-stimulated ATP production, glucose uptake, steady-state mRNA and protein levels of glucose transporters, and cellular activities of glucose-metabolizing enzymes were decreased in rho(0) cells compared with parental rho(+) cells. Our results suggest that the quantitative reduction of mtDNA may suppress the expression of nuclear DNA-encoded glucose transporters and enzymes of glucose metabolism. Thus this may lead to diabetic status, such as decreased ATP production and glucose utilization.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / metabolism
-
Carcinoma, Hepatocellular
-
DNA, Mitochondrial / metabolism*
-
Diabetes Mellitus, Type 1 / genetics
-
Diabetes Mellitus, Type 1 / metabolism
-
Electron Transport Complex IV / genetics
-
Electron Transport Complex IV / metabolism
-
Enzyme Inhibitors / pharmacology
-
Ethidium / pharmacology
-
Glucose / pharmacokinetics*
-
Glucosephosphate Dehydrogenase / metabolism
-
Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
-
Humans
-
Hypoglycemic Agents / pharmacology
-
Insulin / pharmacology
-
Liver Neoplasms
-
Mitochondria / drug effects
-
Mitochondria / enzymology
-
Monosaccharide Transport Proteins / genetics
-
Monosaccharide Transport Proteins / metabolism*
-
Oxidative Phosphorylation / drug effects*
-
Tumor Cells, Cultured
Substances
-
DNA, Mitochondrial
-
Enzyme Inhibitors
-
Hypoglycemic Agents
-
Insulin
-
Monosaccharide Transport Proteins
-
Adenosine Triphosphate
-
Glucosephosphate Dehydrogenase
-
Glyceraldehyde-3-Phosphate Dehydrogenases
-
Electron Transport Complex IV
-
Ethidium
-
Glucose