title: Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice.
abstract: Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation. Exercise improved the capacity for muscle and liver to oxidize palmitate in old mice, but not young mice. In the brain, exercise increased rates of respiration and reactive oxygen species (ROS) production in the old group only while utilizing complex I substrates, effects that were not seen in the young group. Coupled complex I to III enzymatic activity was significantly increased in old trained versus untrained mice with no effect on coupled II to III enzymatic activity. Mitochondrial protein content and markers of mitochondrial biogenesis (PGC-1α and TFAM) were not affected by exercise training in the brain, in contrast to the skeletal muscle of old mice. Brain levels of the autophagy marker LC3-II and protein levels of other signaling proteins that regulate metabolism or transport (BDNF, HSP60, phosphorylated mTOR, FNDC5, SIRT3) were not significantly altered. Old exercised mice showed a significant increase in DRP1 protein levels in the brain without changes in phosphorylation, while MFN2 and OPA1 protein levels were unchanged. Our results suggest that exercise training in old mice can improve brain mitochondrial function through effects on electron transport chain function and mitochondrial dynamics without increasing mitochondrial biogenesis.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, United States; Department of Neurology, NewYork-Presbyterian Hospital, Weill Cornell Medical College, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gusdon
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Callio
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, United States; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, United States.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Distefano
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: O'Doherty
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, United States; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, United States.
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, United States; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, United States. Electronic address: Paul.Coen@flhosp.org.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coen
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, United States. Electronic address: ctc4@pitt.edu.
authors.forename: Charleen T
authors.initials: CT
authors.lastname: Chu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D001678:Organelle Biogenesis; D010805:Physical Conditioning, Animal; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C486391:Dnm1l protein, mouse; D034281:Dynamins; D042967:Electron Transport Complex I
keywords: Brain; Complex I; Cortex; DRP1; Exercise; Mitochondria