Mitochondrial Calcium and the Permeability Transition in Cell Death
By J. Lemasters, T. Theruvath, Zhi Zhong, A. Nieminen. Biochimica et Biophysica Acta, 2009
668 citations recorded by the source corpus.
Dysregulation of Ca2+ has long been implicated to be important in cell injury. A Ca2+-linked process important in necrosis and apoptosis (or necrapoptosis) is the mitochondrial permeability transition (MPT). In the MPT, large conductance permeability transition (PT) pores open that make the mitochondrial inner membrane abruptly permeable to solutes up to 1500 Da. The importance of Ca2+ in MPT induction varies with circumstance. Ca2+ overload is sufficient to induce the MPT. By contrast after ischemia-reperfusion to cardiac myocytes, Ca2+ overload is the consequence of bioenergetic failure after the MPT rather than its cause. In other models, such as cytotoxicity from Reye-related agents and storage-reperfusion injury to liver grafts, Ca2+ appears to be permissive to MPT onset. Lastly in oxidative stress, increased mitochondrial Ca2+ and ROS generation act synergistically to product the MPT and cell death. Thus, the exact role of Ca2+ for inducing the MPT and cell death depends on the particular biologic setting.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/033a55b9d2e1c7048344dc59a3dfa1a75420b83b
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Citations in the corpus
- Initiation and perpetuation of NLRP3 inflammasome activation and assembly (2015, background): “While mitochondria have the capacity to buffer ER Ca release, excessive mitochondrial Ca uptake leads to mitochondrial disruption (79, 119).”
- Pathophysiology of Acute Kidney Injury (2012, positive): “Most notably Ca++ can activate MPT in isolated mitochondria from liver hepatocytes (300) or in permeabilized renal tubule cells at concentrations as low as 35–45 μM (145).”
- MICU1 is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake That Regulates Cell Survival (2012, positive): “Ca2+ flux across the inner mitochondrial membrane (IMM) regulates cell bioenergetics, cytoplasmic Ca2+ ([Ca]i) signals and activation of cell death pathways (Balaban, 2009; Denton and McCormack, 1980; Duchen et al., 2008; Gunter and Gunter, 1994; Hajnoczky et al., 1995; Hansford, 1994; Herrington et”