Multiscale Modeling Of The Regulation OF Mitochondrial Function By Metabolites And Ultrastructure




Shukla, Sangeeta

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Mitochondria are responsible for producing ATP, the energy currency in all living cells. To do this, the mitochondria have a complex micro-architecture upon which occur biomolecular processes that break down energy substrate to produce ATP. In heart which is constantly beating, mitochondrial energy metabolism is well regulated, allowing for increases during exercise. Energy metabolism is thought to be regulated both by changes in metabolite concentration as well as the micro-architecture of the cristae which are the folds in the mitochondrial inner membrane. The two questions addressed here are 1) how is calcium in the mitochondria regulated and what effect does this have on energy metabolism and 2) how does the cristae structure contribute to the regulation of energy metabolism. To this end, a multiscale computational modeling approach has been used to integrate experimental information across disparate scales and gain an understanding of the complex dynamics of this system.



Bioinformatics, Systematic biology, Biophysics, Cellular Energy Metabolism, Mitochondrial ATP Production Efficiency, Mitochondrial Calcium Cycling, Mitochondrial Calcium Signaling, Mitochondrial Model, Mitochondrial Spatial Model