Abstract

The compartmentalization of eukaryotic cells into membrane-bound organelles with specific subcellular positioning enables precise spatial and temporal control of cellular functions. While functionally significant mitochondrial localization has been demonstrated in cells such as neurons, it remains unclear how general these cell principles are. Here, we examine the spatial organization of mitochondria within MIN6 pancreatic beta cells under variable glucose conditions. We observe glucose-dependent redistributions of mitochondria, favoring peripheral localization at elevated glucose levels when insulin secretion is also elevated. Our results suggest that active mitochondrial transport along microtubules and calcium activity, but not ATP synthesis, are critical regulators of this redistribution. We derived a mathematical model that suggests that a putative affinity of the mitochondria with the membrane competes with mitochondrial microtubule attachment to play an important role in establishing the mitochondrial spatial patterns we observe. These results suggest that mitochondrial positioning may contribute to optimizing energy delivery in response to local demand, potentially representing a general regulatory mechanism across various cell types.

Committee Chair

Shankar Mukherji

Committee Members

David Piston; Erik Henriksen; Mikhail Tikhonov; Xi Wang

Degree

Doctor of Philosophy (PhD)

Author's Department

Physics

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

7-17-2025

Language

English (en)

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Physics Commons

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