Depletion of mitochondrial DNA alters glucose metabolism in SK-Hep1 cells.
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.
Park
K S
KS
Division of Metabolic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul 122-701, Korea.
Nam
K J
KJ
Kim
J W
JW
Lee
Y B
YB
Han
C Y
CY
Jeong
J K
JK
Lee
H K
HK
Pak
Y K
YK
D000255:Adenosine Triphosphate / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004996:Ethidium / Q000494:pharmacology; D005947:Glucose / Q000493:pharmacokinetics*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008113:Liver Neoplasms; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D000255:Adenosine Triphosphate; D005954:Glucosephosphate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003576:Electron Transport Complex IV; D004996:Ethidium; D005947:Glucose