Mitochondrial Calcium Overload

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In low amounts, free calcium (Ca2+) is beneficial for mitochondrial ATP production. This cation activates three matrix dehydrogenases that fuel proton pumps for ATP synthesis. In high amounts, the mitochondrial inner membrane permeabilizes which turns them into ATP consumers! In the intermediate range, calcium mysteriously inhibits ATP production which is independent from its role at high levels. As calcium touches upon many mitochondrial processes in a variety of ways, studying how this cation affects each process in isolation is suboptimal. In this vein, we will test a system-level theory on how calcium impacts mitochondrial metabolism using computational tools. These tools will be able to predict mitochondrial ATP production across spatiotemporal domains and physiological settings and facilitate inquiries into other intriguing calcium-related cellular phenomena.