title: Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice.
abstract: Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.
authors.affiliation: 1] Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA [2] Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA [3] Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Lin
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pulliam
authors.forename: Sathyaseelan S
authors.initials: SS
authors.lastname: Deepa
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Halloran
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Hussong
authors.forename: Raquel R
authors.initials: RR
authors.lastname: Burbank
authors.forename: Andrew
authors.initials: A
authors.lastname: Bresnen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Natalia
authors.initials: N
authors.lastname: Podlutskaya
authors.forename: Anuradha
authors.initials: A
authors.lastname: Soundararajan
authors.forename: Eric
authors.initials: E
authors.lastname: Muir
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
authors.forename: Alex F
authors.initials: AF
authors.lastname: Bokov
authors.forename: Carlo
authors.initials: C
authors.lastname: Viscomi
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Arlan G
authors.initials: AG
authors.lastname: Richardson
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.forename: Veronica
authors.initials: V
authors.lastname: Galvan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001783:Blood Flow Velocity / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics*; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D005947:Glucose