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A Minimal Model for the Mitochondrial Rapid Mode of Ca2+ Uptake Mechanism

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  • Jason N Bazil
  • Ranjan K Dash

Abstract

Mitochondria possess a remarkable ability to rapidly accumulate and sequester Ca2+. One of the mechanisms responsible for this ability is believed to be the rapid mode (RaM) of Ca2+ uptake. Despite the existence of many models of mitochondrial Ca2+ dynamics, very few consider RaM as a potential mechanism that regulates mitochondrial Ca2+ dynamics. To fill this gap, a novel mathematical model of the RaM mechanism is developed herein. The model is able to simulate the available experimental data of rapid Ca2+ uptake in isolated mitochondria from both chicken heart and rat liver tissues with good fidelity. The mechanism is based on Ca2+ binding to an external trigger site(s) and initiating a brief transient of high Ca2+ conductivity. It then quickly switches to an inhibited, zero-conductive state until the external Ca2+ level is dropped below a critical value (∼100–150 nM). RaM's Ca2+- and time-dependent properties make it a unique Ca2+ transporter that may be an important means by which mitochondria take up Ca2+ in situ and help enable mitochondria to decode cytosolic Ca2+ signals. Integrating the developed RaM model into existing models of mitochondrial Ca2+ dynamics will help elucidate the physiological role that this unique mechanism plays in mitochondrial Ca2+-homeostasis and bioenergetics.

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  • Jason N Bazil & Ranjan K Dash, 2011. "A Minimal Model for the Mitochondrial Rapid Mode of Ca2+ Uptake Mechanism," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-13, June.
    • Handle: RePEc:plo:pone00:0021324
    DOI: 10.1371/journal.pone.0021324
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    References listed on IDEAS

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    1. Yuriy Kirichok & Grigory Krapivinsky & David E. Clapham, 2004. "The mitochondrial calcium uniporter is a highly selective ion channel," Nature, Nature, vol. 427(6972), pages 360-364, January.
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    1. Manhas, Neeraj & Anbazhagan, N., 2021. "A mathematical model of intricate calcium dynamics and modulation of calcium signalling by mitochondria in pancreatic acinar cells," Chaos, Solitons & Fractals, Elsevier, vol. 145(C).

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