Medical College of Wisconsin
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A biophysically based mathematical model for the kinetics of mitochondrial calcium uniporter. Biophys J 2009 Feb 18;96(4):1318-32

Date

02/17/2009

Pubmed ID

19217850

Pubmed Central ID

PMC2717240

DOI

10.1016/j.bpj.2008.11.005

Scopus ID

2-s2.0-62649106276   31 Citations

Abstract

Ca2+ transport through mitochondrial Ca2+ uniporter is the primary Ca2+ uptake mechanism in respiring mitochondria. Thus, the uniporter plays a key role in regulating mitochondrial Ca2+. Despite the importance of mitochondrial Ca2+ to metabolic regulation and mitochondrial function, and to cell physiology and pathophysiology, the structure and composition of the uniporter functional unit and kinetic mechanisms associated with Ca2+ transport into mitochondria are still not well understood. In this study, based on available experimental data on the kinetics of Ca2+ transport via the uniporter, a mechanistic kinetic model of the uniporter is introduced. The model is thermodynamically balanced and satisfactorily describes a large number of independent data sets in the literature on initial or pseudo-steady-state influx rates of Ca2+ via the uniporter measured under a wide range of experimental conditions. The model is derived assuming a multi-state catalytic binding and Eyring's free-energy barrier theory-based transformation mechanisms associated with the carrier-mediated facilitated transport and electrodiffusion. The model is a great improvement over the previous theoretical models of mitochondrial Ca2+ uniporter in the literature in that it is thermodynamically balanced and matches a large number of independently published data sets on mitochondrial Ca2+ uptake. This theoretical model will be critical in developing mechanistic, integrated models of mitochondrial Ca2+ handling and bioenergetics which can be helpful in understanding the mechanisms by which Ca2+ plays a role in mediating signaling pathways and modulating mitochondrial energy metabolism.

Author List

Dash RK, Qi F, Beard DA

Author

Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Algorithms
Animals
Calcium
Calcium Channels
Kinetics
Mitochondria, Heart
Mitochondria, Liver
Models, Biological
Models, Chemical
Rats
Signal Transduction
Thermodynamics
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