{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:12:12Z","timestamp":1791047532097,"version":"4.1.0"},"reference-count":54,"publisher":"The Company of Biologists","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,2,1]]},"abstract":"<jats:p>In normal pancreatic acinar cells, the oxidant menadione evokes repetitive cytosolic Ca2+ spikes, partial mitochondrial depolarisation,cytochrome c release and apoptosis. The physiological agonists acetylcholine and cholecystokinin also evoke cytosolic Ca2+ spikes but do not depolarise mitochondria and fail to induce apoptosis. Ca2+ spikes induced by low agonist concentrations are confined to the apical secretory pole of the cell by the buffering action of perigranular mitochondria. Menadione prevents mitochondrial Ca2+ uptake, which permits rapid spread of Ca2+ throughout the cell. Menadione-induced mitochondrial depolarisation is due to induction of the permeability transition pore. Blockade of the permeability transition pore with bongkrekic acid prevents activation of caspase 9 and 3. In contrast, the combination of antimycin A and acetylcholine does not cause apoptosis but elicits a global cytosolic Ca2+ rise and mitochondrial depolarisation without induction of the permeability transition pore. Increasing the cytosolic Ca2+buffering power by BAPTA prevents cytosolic Ca2+ spiking, blocks the menadione-elicited mitochondrial depolarisation and blocks menadione-induced apoptosis. These results suggest a twin-track model in which both intracellular release of Ca2+ and induction of the permeability transition pore are required for initiation of apoptosis.<\/jats:p>","DOI":"10.1242\/jcs.115.3.485","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T23:33:46Z","timestamp":1619220826000},"page":"485-497","source":"Crossref","is-referenced-by-count":142,"title":["Menadione-induced apoptosis: roles of cytosolic Ca2+elevations and the mitochondrial permeability transition pore"],"prefix":"10.1242","volume":"115","author":[{"given":"Julia V.","family":"Gerasimenko","sequence":"first","affiliation":[{"name":"Medical Research Council Secretory Control Research Group, Physiological Laboratory, University of Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg V.","family":"Gerasimenko","sequence":"additional","affiliation":[{"name":"Medical Research Council Secretory Control Research Group, Physiological Laboratory, University of Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altaf","family":"Palejwala","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Liverpool L69 3BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei V.","family":"Tepikin","sequence":"additional","affiliation":[{"name":"Medical Research Council Secretory Control Research Group, Physiological Laboratory, University of Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole H.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Medical Research Council Secretory Control Research Group, Physiological Laboratory, University of Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair J. 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