Menezes-Filho 2017 Free Radic Biol Med
|Menezes-Filho SL, Amigo I, Prado FM, Ferreira NC, Koike MK, Pinto IFD, Miyamoto S, Montero EFS, Medeiros MHG, Kowaltowski AJ (2017) Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca2+-induced mitochondrial permeability transition. Free Radic Biol Med 110:219-27.|
Abstract: Caloric restriction (CR) promotes lifespan extension and protects against many pathological conditions, including ischemia/reperfusion injury to the brain, heart and kidney. In the liver, ischemia/reperfusion damage is related to excessive mitochondrial Ca2+ accumulation, leading to the mitochondrial permeability transition. Indeed, liver mitochondria isolated from animals maintained on CR for 4 months were protected against permeability transition and capable of taking up Ca2+ at faster rates and in larger quantities. These changes were not related to modifications in mitochondrial respiratory activity, but rather to a higher proportion of ATP relative to ADP in CR liver mitochondria. Accordingly, both depletion of mitochondrial adenine nucleotides and loading mitochondria with exogenous ATP abolished the differences between CR and ad libitum (AL) fed groups. The prevention against permeability transition promoted by CR strongly protected against in vivo liver damage induced by ischemia/reperfusion. Overall, our results show that CR strongly protects the liver against ischemia/reperfusion and uncover a mechanism for this protection, through a yet undescribed diet-induced change in liver mitochondrial Ca2+ handling related to elevated intramitochondrial ATP.
Copyright © 2017 Elsevier Inc. All rights reserved. • Keywords: ATP, Ca(2+), Calorie restriction, Ischemic protection, Liver, Mitochondria • Bioblast editor: Kandolf G • O2k-Network Lab: BR Sao Paulo Kowaltowski AJ
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Stress:Ischemia-reperfusion, Permeability transition Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET