caa a22 4500 606235345 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2491-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2491-2 Identification of functional leptin receptors expressed in ventricular mitochondria [Elektronische Daten] [Eduardo Martinez-Abundis, Venkatesh Rajapurohitam, Arieh Gertler, Morris Karmazyn] Leptin is a 16kDa pro-satiety peptide produced primarily not only by white adipocytes but also by numerous other tissues including the heart. Circulating leptin exerts its effect through specific receptors, although its principle actions are dependent on the activation of the long form of the leptin receptor, termed OBRb. As leptin is also produced within the cardiomyocyte, we hypothesized that the peptide can also exert effects by targeting intracellular sites. Accordingly, we determined whether cardiac mitochondria express functional leptin receptors. The presence of mitochondrial OBRb was identified through Western blotting of isolated mitochondria, immunofluorescence as well as immunogold labeling with electron microscopy. Although leptin had no direct effect on mitochondrial integrity, it profoundly enhanced the ability of calcium to induce mitochondrial swelling, an effect partially reversed by an OBR antagonist. 24h exposure to leptin (50ng/ml) was without effect on mitochondria in cultured neonatal rat ventricular myocytes in contrast to leptin tagged with a 10 amino acid membrane translocation sequence which significantly induced mitochondrial permeability transition pore opening, whereas both leptins produced a hypertrophic response. Our results therefore show that mitochondria express functional OBR which may be of importance toward understanding the role of intracellularly derived leptin in cardiac physiology and pathology. Springer Science+Business Media New York, 2015 Heart nationallicence Mitochondria nationallicence Mitochondrial OBR expression nationallicence Mitochondrial swelling nationallicence Martinez-Abundis Eduardo Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut Rajapurohitam Venkatesh Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut Gertler Arieh Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel aut Karmazyn Morris Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 155-162 0300-8177 408:1-2<155 2015 408 11010 https://doi.org/10.1007/s11010-015-2491-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2491-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Martinez-Abundis Eduardo Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut NATIONALLICENCE 700 1- Rajapurohitam Venkatesh Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut NATIONALLICENCE 700 1- Gertler Arieh Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel aut NATIONALLICENCE 700 1- Karmazyn Morris Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, ON, Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 155-162 0300-8177 408:1-2<155 2015 408 11010