New U01 Awardee Presentation

Title: Multiscale studies of mitochondrial calcium cycling

Abstract:

Mitochondria have a complex structure consisting of an outer membrane and a highly folded inner membrane which forms cristae. The protein complexes responsible for energy metabolism are located in the inner membrane with varying distributions depending upon species and physiological or pathological conditions.  We are using a joint multi-scale modeling and experimental approach to study how the mitochondrial inner membrane geometry affects function.  Our modeling studies have indicated that gradients of chemical species, reactants and products, including Ca²⁺, form along the length of the cristae.  Here we specifically study the spatio-temporal Ca²⁺ dynamics of the mitochondria and the impact that the Ca²⁺ distribution may have on energy metabolism.  Two schools of thought exist in the experimental literature as to whether mitochondrial Ca²⁺   cycling is fast or slow.  The consequences of fast Ca²⁺ cycling is that Ca²⁺ fluxes across the mitochondrial inner membrane are large leading to large fluctuations in mitochondrial [Ca²⁺].  Conversely, slow Ca²⁺ cycling results in small transmembrane Ca²⁺ fluxes and small transient changes in mitochondrial [Ca²⁺]. We use a hierarchy of models and experimental approaches to differentiate between the two modes of Ca²⁺ cycling and the potential consequences for energy metabolism.  The model also suggests why the two competing modes of Ca²⁺ cycling appear in the scientific literature.

Biosketch:

Saleet Jafri, Department of Molecular Neuroscience and School of Systems Biology, George Mason University, Farifax VA 22030

Carmen Mannella, Wadsworth Center, New York State Department of Health, Albany NY 12201

Jon Lederer, Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore MD 21201

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