Open AccessDepletion of mitochondrial DNA alters glucose metabolism in SK-Hep1 cells
Author(s) -
KyuSang Park,
Kyung-Jay Nam,
JunWoo Kim,
YounBok Lee,
Chang-Yeop Han,
June-Key Jeong,
Hong-Kyu Lee,
Youngmi Kim Pak
Publication year - 2001
Publication title -
ajp endocrinology and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.507
H-Index - 201
eISSN - 1522-1555
pISSN - 0193-1849
DOI - 10.1152/ajpendo.2001.280.6.e1007
Subject(s) - mitochondrial dna , intracellular , ethidium bromide , metabolism , mitochondrion , carbohydrate metabolism , glucose transporter , enzyme , biology , glucose uptake , stimulation , dna , biochemistry , medicine , endocrinology , gene , insulin
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.
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