Mitochondrial Ca2+ dynamics in cells and suspensions. 2017

Benjamin Wacquier, and Hugo E Romero Campos, and Virginia González-Vélez, and Laurent Combettes, and Geneviève Dupont
Unité de Chronobiologie Théorique, Université Libre de Bruxelles, Belgium.

Mitochondria play a significant role in shaping cytosolic Ca2+ signals. Thus, transfer of Ca2+ across the mitochondrial membrane is much studied, not only in intact cells but also in artificial systems such as mitochondrial suspensions or permeabilised cells. Observed rates of Ca2+ changes vary by at least one order of magnitude. In this work, we investigate the relationship between the Ca2+ dynamics observed in various experimental conditions using a computational model calibrated on experimental data. Results confirm that mitochondrial Ca2+ exchange fluxes through the mitochondrial Ca2+ uniporter (MCU) and the Na+ /Ca2+ exchanger obey the same basic kinetics in cells and in suspensions, and emphasise the important role played by the high Ca2+ levels reached in mitochondria-associated endoplasmic reticulum membranes in intact cells. Tissue specificity can be ascribed to the different modes of regulation of the MCU by Ca2+ , probably related to the specific levels of expression of the Ca2+ sensing regulator subunit of this channel. The model emphasises the importance of mitochondrial density and buffering in controlling the rate of Ca2+ exchanges with mitochondria, as verified experimentally. Finally, we show that heterogeneity between individual mitochondria can explain the large range of amplitudes and rates of rise in mitochondrial Ca2+ concentration that have been observed experimentally.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
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
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
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
D013535 Suspensions Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (AEROSOLS) and other colloidal systems; water-insoluble drugs may be given as suspensions. Suspension
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels
D051336 Mitochondrial Membranes The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE). Inner Mitochondrial Membrane,Mitochondrial Membrane, Inner,Mitochondrial Membrane, Outer,Outer Mitochondrial Membrane,Inner Mitochondrial Membranes,Membrane, Inner Mitochondrial,Membrane, Mitochondrial,Membrane, Outer Mitochondrial,Membranes, Inner Mitochondrial,Membranes, Mitochondrial,Membranes, Outer Mitochondrial,Mitochondrial Membrane,Mitochondrial Membranes, Inner,Mitochondrial Membranes, Outer,Outer Mitochondrial Membranes

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