We have investigated in detail the role of intra-organelle Ca2+ content during induction of apoptosis by the oxidant menadione while changing and monitoring Ca2+ load of ER, mitochondria and acidic organelles. Menadione causes production of reactive oxygen species, induction of oxidative stress and subsequently apoptosis. In both pancreatic acinar and pancreatic tumour AR42J cells, menadione was found to induce repetitive cytosolic Ca2+ responses due to release of Ca2+ from both ER and acidic stores. Ca2+ responses to menadione were accompanied by elevation of Ca2+ in mitochondria, mitochondrial depolarisation and mPTP opening. Emptying of both the ER and acidic Ca2+ stores did not necessarily prevent menadione-induced apoptosis. High mitochondrial Ca2+ at the time of menadione application was the major factor determining cell fate. However, if mitochondria were prevented from loading with Ca2+, then apoptosis did not occur irrespectively of other Ca2+ stores’ content. These results were confirmed by ratiometric measurements of intra-mitochondrial Ca2+ with pericam. We conclude that elevated Ca2+ in mitochondria is the crucial factor in determining whether cells undergo oxidative stress-induced apoptosis.
University College Dublin (2009) Proc Physiol Soc 15, C20
Oral Communications: Calcium elevation in mitochondria is the main Ca2+ requirement for mPTP opening
O. Gerasimenko1, H. K. Baumgartner1,2, J. V. Gerasimenko1, C. Thorne1, T. Pozzan4, A. V. Tepikin1, O. H. Petersen1, R. Sutton3, A. J. Watson2
1. Physiology, Liverpool University, Liverpool, United Kingdom. 2. Division of Gastroenterology, Liverpool University, Liverpool, United Kingdom. 3. Division of Surgery and Oncology, Liverpool University, Liverpool, United Kingdom. 4. Biomedical Sciences and CNR Institute of Neurosciences, University of Padua, Padua, Italy.
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Where applicable, experiments conform with Society ethical requirements.