Date Degree Awarded

Summer 7-28-2020

Degree Type

Open Access Dissertation

Degree Name

PHD in Applied Life Sciences

First Thesis/Dissertation Advisor

Jeniffer Hernandez, PhD

Second Thesis/Dissertation Advisor

Derick Han, PhD

Third Thesis/Dissertation Advisor

Jerome Garcia, PhD

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Abstract

Mitochondria are dynamic, double-membrane bound hubs of bioenergetics, cell signaling, and redox balance that exist as an oscillating network of fused superstructures and smaller, single organelles. Importantly, their position at the junction of catabolic and anabolic metabolism connects these morphological fluctuations to larger cellular metabolic programs, which in turn have implicated mitochondrial dynamics in a number of disease states and a varied set of cell phenomena. For example, differentiation of memory t-cells is dependent on mitochondrial network morphology, and in particular on remodeling dynamics that yield fused mitochondrial assemblies favoring oxidative phosphorylation-driven metabolism. In contrast, many cancers have been shown to de- emphasize mitochondrial fusion processes through enhanced fission action, which has been theorized to be associated with the glycolytic hallmarks of cancer proliferation and progression. This dissertation elucidates the diversity of roles mitochondrial dynamics and bioenergetics play in defining molecular metabolic schemes across many normal and abnormal physiologies, and underscores the importance of the original research we have produced within the immunological, oncological, and hepatic domains. In particular, the through-lines of our findings on mitochondrial plasticity and remodeling in cancer chemotherapy survival mechanisms, t-cell fate, obesity, and hepatocyte injury will be discussed and explored in-depth from an integrated and translational perspective.

Rights Information

© 2020 Carl W. Decker

COinS