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(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
Author(s):
Chweih, Hanan [1] ; Castilho, Roger F. [1] ; Figueira, Tiago R. [1]
Total Authors: 3
Affiliation:
[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
Abstract

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: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
Grantee:Aníbal Eugênio Vercesi
Support Opportunities: Research Projects - Thematic Grants
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 Opportunities: Scholarships in Brazil - Post-Doctoral