nhanced resistance to Ca2+-induced mitochondrial permeability transition in the long-lived red-footed tortoise Chelonoidis carbonari

Author(s)

Sartori, Marina R. ^[1] ; Navarro, Claudia D. C. ^[1] ; Castilho, Roger F. ^[1] ; Vercesi, Anibal E. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Dept Pathol, BR-13083887 Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Experimental Biology; v. 225, n. 1 JAN 2022.
• Web of Science Citations: 0

Abstract

The interaction between supraphysiological cytosolic Ca2+ levels and mitochondrial redox imbalance mediates the mitochondrial permeability transition (MPT). The MPT is involved in cell death, diseases and aging. This study compared the liver mitochondrial Ca2+ retention capacity and oxygen consumption in the long-lived red-footed tortoise (Chelonoidis carbonada) with those in the rat as a reference standard. Mitochondrial Ca2+ retention capacity, a quantitative measure of MPT sensitivity, was remarkably higher in tortoises than in rats. This difference was minimized in the presence of the MPT inhibitors ADP and cyclosporine A. However, the Ca2+ retention capacities of tortoise and rat liver mitochondria were similar when both MPT inhibitors were present simultaneously. NADH-linked phosphorylating respiration rates of tortoise liver mitochondria represented only 30% of the maximal electron transport system capacity, indicating a limitation imposed by the phosphorylation system. These results suggested underlying differences in putative MPT structural components {[}e.g. ATP synthase, adenine nucleotide translocase (ANT) and cyclophilin D] between tortoises and rats. Indeed, in tortoise mitochondria, titrations of inhibitors of the oxidative phosphorylation components revealed a higher limitation of ANT. Furthermore, cyclophilin D activity was approximately 70% lower in tortoises than in rats. Investigation of critical properties of mitochondrial redox control that affect MPT demonstrated that tortoise and rat liver mitochondria exhibited similar rates of H2O2 release and glutathione redox status. Overall, our findings suggest that constraints imposed by ANT and cyclophilin D, putative components or regulators of the MPT pore, are associated with the enhanced resistance to Ca2+-induced MPT in tortoises. (AU)

• FAPESP's process: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases
• Grantee: Aníbal Eugênio Vercesi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/20855-7 - The role of mitochondrial NAD(P)-Transhydrogenase in the development of Fatty Liver Disease and aging in mice
• Grantee: Claudia Daniele Carvalho Navarro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/05487-6 - Mitochondrial function and molecular markers associated with aging in the long-lived red-footed tortoise Chelonoidis carbonaria
• Grantee: Marina Rincon Sartori
• Support Opportunities: Scholarships in Brazil - Post-Doctoral