Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Tissue and sex specificities in Ca2+ handling by isolated mitochondria in conditions avoiding the permeability transition

Full text
Chweih, Hanan [1] ; Castilho, Roger F. [1] ; Figueira, Tiago R. [1]
Total Authors: 3
[1] Univ Estadual Campinas, Dept Clin Pathol, Fac Med Sci, Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Experimental Physiology; v. 100, n. 9, p. 1073-1092, SEP 1 2015.
Web of Science Citations: 10

New Findings What is the central question of this study? The assessment of Ca2+ handling by isolated mitochondria can be biased by dysfunctions secondary to Ca2+-induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca2+ transport are still unsettled questions. What is the main finding and its importance? If MPT is not prevented during Ca2+ transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca2+ handling, particularly in the Ca2+ efflux pathways. The characteristics of mitochondria, including their Ca2+ transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca2+-induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca2+ transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca2+ and the rates of mitochondrial Ca2+ efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca2+, Mg2+ and Na+. The Ca2+ influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca2+ efflux rates exhibited more tissue diversity, especially in the presence of Na+. Interestingly, the Na+-independent Ca2+ efflux was highest in the heart mitochondria (approximate to 4nmolmg(-1)min(-1)), thus challenging the view that cardiac mitochondrial Ca2+ efflux relies almost exclusively on a Na+-dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca2+ homeostasis and in the ADP-stimulated respiration of liver mitochondria (approximate to 20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca2+ handling by isolated mitochondria. (AU)

FAPESP's process: 11/51800-1 - Muscle damage induced by eccentric exercise: involvement of mitochondria and interactions with statin myotoxicity
Grantee:Tiago Rezende Figueira
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
Grantee:Aníbal Eugênio Vercesi
Support type: Research Projects - Thematic Grants