25th Northern Cardiovascular Research Group (NCRG) meeting
This year’s meeting is co-hosted by The University of Manchester and The University of Salford and will be held at the Sackville Street Building, North Campus, The University of Manchester.
Cairn Research Keynote Lecture
We are pleased to announce Dr Elizabeth Murphy (Maryland, USA) will be presenting the Cairn Research Keynote Lecture, “Mitochondria: Regulators of life and death”.
Mitochondrial Permeability Transition Pore: Regulation by Calcium and Post-Translational Modifications
Elizabeth Murphy, Randi J. Parks, Sara Menazza, Julia C. Liu, Jie Liu and Toren Finkel, NHLBI, NIH, Bethesda, MD
Mitochondria play a key role in cell death in cardiac ischemia and reperfusion. An increase in mitochondrial calcium occurring via calcium uptake by the mitochondrial calcium uniporter (MCU) is thought to trigger opening of a large conductance channel in the inner mitochondrial member known as the permeability transition pore.
To investigate the role of the MCU in regulating mitochondrial calcium, metabolism and cell death we studied mice lacking the MCU. Mitochondria from WT mice rapidly accumulated calcium; however on addition of calcium to mitochondria from the MCU-KO hearts there was no calcium uptake, suggesting that if alternative calcium uptake pathways are present, they must be very slow, as no calcium uptake occurred over a 10 to 20 minute time scale. Mitochondria from MCU-KO hearts did not exhibit swelling associated with opening of the mitochondrial permeability transition pore (PTP) on addition of high levels of calcium, which led to pore opening in WT mitochondria.
Surprisingly, perfused hearts from MCU-KO mice subjected to ischemia and reperfusion had showed no difference in infarct size or in recovery of contractile function compared to WT hearts. It is possible that the PTP is activated in the MCU-KO hearts in a calcium independent manner. If PTP activation occurs in MCU-KO heart, then cyclosporine A (CsA), an inhibitor of the PTP, should provide protection in the MCU-KO hearts. However, WT hearts were protected from ischemia-reperfusion cell death by the administration of CsA, but MCU-KO hearts were not. Thus in contrast to the WT hearts, inhibition of the PTP is not protective in the MCU-KO hearts. These data suggest loss of MCU before birth may lead to compensatory changes.
We investigated the hypothesis that the lack of protection in the absence of MCU may be explained by compensatory changes in mitochondrial protein complexes and post-translational modifications. We have previously shown that acute signaling can initiate cardioprotection, suggesting the PTP opening is regulated by post-translational modifications.
Following the day’s events, the meeting will conclude with a meal at Swadesh Indian Restaurant.
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Registration and abstract submission
Download a registration form and instructions here.
Download a copy of the NCRG2017 programme (PDF).
Maps and travel
The venue for our meeting is Sackville Street Building, North Campus, The University of Manchester, M1 3BB.
Click here for travel information and maps to help you find us.
Our NCRG conference dinner will be held at Swadesh Indian Restaurant and costs £10.
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We are grateful to the following organisations for their generous sponsorship. Please make every effort to check out these links and visit exhibitors on the day.