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Mechanisms and physiological implications of mitochondrial and cellular calcium signaling

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MacEwen, Melissa Jane

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Abstract

Calcium signaling is central to fields as disparate as memory formation, protein structure, and cellular migration. The five chapters of this dissertation each examine calcium signaling in a different context. First, an introduction contextualizes this dissertation in the broader history of calcium signaling and mitochondrial biology. Second, a published review details the most salient contributions to the field of mitochondrial calcium signaling in recent years. Third, a research publication clarifies why the metazoan mitochondrial calcium uniporter (MCU) requires another protein, EMRE, to conduct calcium ions. The fourth chapter provides an overview of an ongoing research project examining potential metabolic “rewiring” that enables mitochondria to produce energy and metabolites even when mitochondrial calcium signaling is compromised. Finally, the fifth chapter showcases a research publication that used experimental biochemistry to determine which of three proposed mathematical models most accurately reflects the binding between calmodulin (CaM) and myosin light-chain kinase (MLCK).

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Thesis (Ph.D.)--University of Washington, 2023

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