Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca2+- induced mitochondrial permeability transition

Author(s)

Menezes-Filho, Sergio L. ; Amigo, Ignacio ; Prado, Fernanda M. ; Ferreira, Natalie C. ; Koike, Marcia K. ; Pinto, Isabella F. D. ; Miyamoto, Sayuri ; Montero, Edna F. S. ; Medeiros, Marisa H. G. ; Kowaltowski, Alicia J.

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 110, p. 219-227, SEP 2017.
• Web of Science Citations: 9

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. (AU)

• FAPESP's process: 12/50500-7 - Involvement of the RTG-dependent retrograde signaling pathway in the maintenance of mitochondrial activity during ageing in Saccharomyces cerevisiae
• Grantee: Fernanda Marques da Cunha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/11556-2 - Cardiolipin in neurodegenerative diseases: characterization of oxidized products and modified proteins in a model of Amyotrophic Lateral Sclerosis
• Grantee: Isabella Fernanda Dantas Pinto
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)