Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. 2003

Jae-Sung Kim, and Lihua He, and John J Lemasters
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, CB#7090, 236 Taylor Hall, Chapel Hill, NC 27599-7090, USA.

Opening of high conductance permeability transition pores in mitochondria initiates onset of the mitochondrial permeability transition (MPT). The MPT is a causative event, leading to necrosis and apoptosis in hepatocytes after oxidative stress, Ca(2+) toxicity, and ischemia/reperfusion. CsA blocks opening of permeability transition pores and protects cell death after these stresses. In contrast to necrotic cell death which is a consequence of ATP depletion, ATP is required for the development of apoptosis. Reperfusion and the return of normal pH after ischemia initiate the MPT, but the balance between ATP depletion after the MPT and ATP generation by glycolysis determines whether the fate of cells will be apoptotic or necrotic death. Thus, the MPT is a common pathway leading to both necrotic and apoptotic cell death after ischemia/reperfusion.

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000083162 Mitochondrial Permeability Transition Pore A multiprotein inner mitochondrial complex which opens only under certain pathological conditions (e.g., OXIDATIVE STRESS) uncoupling the membrane leading to APOPTOSIS and MITOCHONDRIAL TRANSMEMBRANE PERMEABILITY-DRIVEN NECROSIS particularly in CARDIOMYOCYTES during MYOCARDIAL REPERFUSION INJURY. Mitochondrial Megachannel,Mitochondrial Permeability Transition Pore (mPTP),mPTP Protein
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries

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