title: Heat shock protein 70 (Hsp70) inhibits oxidative phosphorylation and compensates ATP balance through enhanced glycolytic activity.
abstract: To address possible effects of heat shock protein 70 (Hsp70) on energy metabolism, we established a cell line expressing different levels of Hsp70 and evaluated changes in glucose and lactate metabolites, as well as ATP levels accordingly. In addition, activities of enzymes involved in glycolysis [phosphofructokinase (PFK) and lactate dehydrogenase (LDH)], Krebs cycle [citric synthase (CS)], and oxidative phosphorylation {NADH dehydrogenase [complex I (CI)] and ubiquinol:cytochrome-c reductase [complex III (CIII)]} were analyzed. The results show that both glucose consumption and lactate excretion were elevated significantly in cells expressing increased levels of Hsp70. Simultaneously, the activities of glycolytic enzymes PFK and LDH were increased markedly in cells overexpressing Hsp70. Activities of enzymes CI and CIII, both involved in oxidative phosphorylation, decreased upon increased expression of Hsp70. These findings were supported by nonsignificant reductions of CS activities in cells that overexpressed Hsp70, whereas intracellular ATP levels remained constant over a wide range of Hsp70 expression. In conclusion, overexpression of Hsp70 in HeLa cells results in downregulation of oxidative phosphorylation, in particular, multiprotein CIII, the main source of reactive oxygen species. In exchange, upregulation of the glycolytic pathway compensates for the homeostasis of cellular ATP supply.
authors.affiliation: Section of Sports and Rehabilitation Medicine, Department of Internal Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Liangli
authors.initials: L
authors.lastname: Wang
authors.forename: Uwe
authors.initials: U
authors.lastname: Schumann
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Liu
authors.forename: Olga
authors.initials: O
authors.lastname: Prokopchuk
authors.forename: Jürgen M
authors.initials: JM
authors.lastname: Steinacker
mesh_terms: D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002952:Citric Acid Cycle; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D025221:Phosphofructokinases / Q000378:metabolism; D014162:Transfection
chemical_list: D018840:HSP70 Heat-Shock Proteins; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; D025221:Phosphofructokinases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005947:Glucose