Journal article

Publication year: 2017

Journal: Basic Research in Cardiology

Volume number: 112

Issue number: 3

ISSN: 0300-8428

eISSN: 1435-1803

DOI Link: https://doi.org/10.1007/s00395-017-0618-1

Publisher: Springer

Abstract: 
Mitochondrial connexin 43 (Cx43) plays a key role in cardiac cytoprotection caused by repeated exposure to short periods of non-lethal ischemia/reperfusion, a condition known as ischemic preconditioning. Cx43 also forms calcium (Ca2+)-permeable hemichannels that may potentially lead to mitochondrial Ca2+ overload and cell death. Here, we studied the role of Cx43 in facilitating mitochondrial Ca2+ entry and investigated its downstream consequences. To that purpose, we used various connexin-targeting peptides interacting with extracellular (Gap26) and intracellular (Gap19, RRNYRRNY) Cx43 domains, and tested their effect on mitochondrial dye- and Ca2+-uptake, electrophysiological properties of plasmalemmal and mitochondrial Cx43 channels, and cell injury/cell death. Our results in isolated mice cardiac subsarcolemmal mitochondria indicate that Cx43 forms hemichannels that contribute to Ca2+ entry and may trigger permeability transition and cell injury/death. RRNYRRNY displayed the strongest effects in all assays and inhibited plasma membrane as well as mitochondrial Cx43 hemichannels. RRNYRRNY also strongly reduced the infarct size in ex vivo cardiac ischemia-reperfusion studies. These results indicate that Cx43 contributes to mitochondrial Ca2+ homeostasis and is involved in triggering cell injury/death pathways that can be inhibited by RRNYRRNY peptide.

Harvard Citation style: Gadicherla, A., Wang, N., Bulic, M., Agullo-Pascual, E., Lissoni, A., De Smet, M., et al. (2017) Mitochondrial Cx43 hemichannels contribute to mitochondrial calcium entry and cell death in the heart, Basic Research in Cardiology, 112(3), Article 27. https://doi.org/10.1007/s00395-017-0618-1

APA Citation style: Gadicherla, A., Wang, N., Bulic, M., Agullo-Pascual, E., Lissoni, A., De Smet, M., Delmar, M., Bultynck, G., Krysko, D., Camara, A., Schlueter, K., Schulz, R., Kwok, W., & Leybaert, L. (2017). Mitochondrial Cx43 hemichannels contribute to mitochondrial calcium entry and cell death in the heart. Basic Research in Cardiology. 112(3), Article 27. https://doi.org/10.1007/s00395-017-0618-1