Pyk2 Expression and Localization in Cardiac Mitochondria and Its Role in Mitochondrial Calcium Regulation
Ariele Baggett, Celia Fernandez-Sanz, Sergio De La Fuente, Johannes Hoek, and Shey-Shing Sheu
TRPM2 is a non-selective cation channel located in the plasma membrane of the cell. Upon activation, the channel opens, allowing calcium to enter into the cytosol of the cell, leading ultimately to the phosphorylation and activation of the enzyme Pyk2 (proline-rich tyrosine kinase 2). Once phosphorylated, Pyk2 translocates from the cytosol to the mitochondria, where it regulates the formation of the pore component of the mitochondrial calcium uniporter (MCU) complex. Consequently, this interaction is a key factor in mitochondrial calcium uptake and therefore mitochondrial bioenergetics.
Karina Cuevas-Mora, Dominic Sales, Hoora Shaghaghi, Ross Summer, and Freddy Romero
To determine whether mitochondrial function and/or the proteasome system is altered in fibroblasts from the HPS mouse lung.
Stephen Hurst, Ludovic Gomez, and Shey-Shing Sheu
Mitochondrial calcium overload and oxidative stress during ischemia reperfusion (I/R) injury remains a major obstacle during percutaneous coronary intervention after acute myocardial infarction. It often leads to an increased susceptibility for mitochondria permeability transition pore (mPTP) opening leading to cell death. Mitochondrial calcium overload and ROS have been identified as key triggers to open the mPTP for over 30 years, yet the exact mechanism has remained elusive. Additionally, glycogen synthase kinase 3β; (GSK-3β;) is proposed as one of the key molecules that regulate mitochondrial dysfunction and injury during I/R. Indeed inhibition of GSK-3β has been shown to be required for ischemic pre- and postconditioning. Interestingly inhibition of GSK-3β is detrimental during the ischemic phase but beneficial only during the reperfusion stage of I/R injury.
- Identify the GSK-3β mediated phosphorylation site(s) on CypD
- Identify the key mechanism of site-specific phosphorylation of CypD on mPTP regulation in the context of Ischemia Reperfusion Injury
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