Amigo 2016 Aging Cell
|Amigo I, Menezes-Filho SL, Luévano-Martínez LA, Chausse B, Kowaltowski AJ (2016) Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. Aging Cell 16:73-81.|
Abstract: Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain. These changes are accompanied by a decrease in cyclophilin D activity and acetylation and an increase in Sirt3 expression. This suggests that Sirt3-mediated deacetylation and inhibition of cyclophilin D in CR promote the inhibition of mitochondrial permeability transition, resulting in enhanced mitochondrial calcium retention. Altogether, our results indicate that enhanced mitochondrial calcium retention capacity underlies the beneficial effects of CR against excitotoxic conditions. This protection may explain the many beneficial effects of CR in the aging brain.
© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
• Keywords: Aging, Brain, Calcium, Caloric restriction, Mitochondria
• O2k-Network Lab: BR Sao Paulo Kowaltowski AJ
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Mouse Tissue;cell: Nervous system Preparation: Isolated mitochondria Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase Regulation: Calcium Coupling state: LEAK, OXPHOS, ET Pathway: N, S HRR: Oxygraph-2k