title: Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity.
abstract: Calorie restriction (CR) has been shown to increase lifespan and delay aging phenotypes in many diverse eukaryotic species. In mouse models of Alzheimer's disease (AD), CR has been shown to decrease amyloid-beta and hyperphosphorylated tau levels and preserve cognitive function. Overexpression of human mutant tau protein has been shown to induce deficits in mitochondrial electron transport chain complex I activity. Therefore, experiments were performed to determine the effects of 4-month CR on brain mitochondrial function in Tg4510 mice, which express human P301L tau. Expression of mutant tau led to decreased ADP-stimulated respiratory rates, but not uncoupler-stimulated respiratory rates. The membrane potential was also slightly higher in mitochondria from the P301L tau mice. As shown previously, tau expression decreased mitochondrial complex I activity. The decreased complex I activity, decreased ADP-stimulated respiratory rate, and increased mitochondrial membrane potential occurring in mitochondria from Tg4510 mice were not restored by CR. However, the CR diet did result in a genotype independent decrease in mitochondrial F0F1-ATPase activity. This decrease in F0F1-ATPase activity was not due to lowered levels of the alpha or beta subunits of F0F1-ATPase. The possible mechanisms through which CR reduces the F0F1-ATPase activity in brain mitochondria are discussed.
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Vedad
authors.initials: V
authors.lastname: Delic
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL 33613, United States; USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States.
authors.forename: Milene
authors.initials: M
authors.lastname: Brownlow
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL 33613, United States; USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Joly-Amado
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zivkovic
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Kenyaria
authors.initials: K
authors.lastname: Noble
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Tam-Anh
authors.initials: TA
authors.lastname: Phan
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Yen
authors.initials: Y
authors.lastname: Ta
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bell
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Crupa
authors.initials: C
authors.lastname: Kurien
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Reynes
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL 33613, United States; USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, United States. Electronic address: pbradsha@usf.edu.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Bradshaw
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D019069:Cell Respiration; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016875:tau Proteins; D006180:Proton-Translocating ATPases
keywords: ATP synthase; Alzheimer's; Calorie restriction; Complex I; Mitochondria; Tau