title: Polymerase gamma mutator mice rely on increased glycolytic flux for energy production.
abstract: Several studies have illustrated that the polymerase gamma mutator (PolG) mice have reduced mitochondrial content secondary to systemic mitochondrial dysfunction, and subsequently a lower capacity to perform aerobic respiration and endurance exercise. We sought to delineate the extent of glycolysis as a means of energy production in the PolG mice in the absence of optimal mitochondrial function. PolG mice display an enhanced reliance on glycolysis as compared to their wild-type counterparts. This is evident by the resting hypoglycemia, higher PFK content, and elevated plasma lactate levels in the PolG mice. In vitro experiments provide further proof that PolG derived dermal fibroblasts have a higher rate of, and capacity for, glycolysis. PolG mice also have enhanced capacity to perform hepatic gluconeogenesis that is likely enhancing the Cori cycle capacity.
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Saleem
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Adeel
authors.initials: A
authors.lastname: Safdar
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kitaoka
authors.affiliation: Department of Medicine, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Olivia S
authors.initials: OS
authors.lastname: Marquez
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Akhtar
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Aisha
authors.initials: A
authors.lastname: Nazli
authors.affiliation: Department of Kinesiology, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Rahul
authors.initials: R
authors.lastname: Suri
authors.affiliation: Department of Medicine, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Turnbull
authors.affiliation: Department of Pediatrics, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada; Department of Medicine, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada; Department of Kinesiology, McMaster University, 1200 Main St. West, Hamilton, ON, L8N 3Z5, Canada. Electronic address: tarnopol@mcmaster.ca.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000818:Animals; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency*; D004734:Energy Metabolism; D006019:Glycolysis; D064688:Metabolic Flux Analysis; D008810:Mice, Inbred C57BL; D028361:Mitochondrial Diseases / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse
keywords: GTT; Gluconeogenesis; Glycolysis; Lactate; Polymerase gamma mice