Mitochondria in Local Control of Programmed Cell Killing & Resilience

Author

• Rashna Sharmin, University of Texas at ArlingtonFollow

Graduation Semester and Year

Spring 2026

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biology

Department

Biology

First Advisor

Piya Ghose

Abstract

Specialized cells are commonplace and defined by different compartments. Organelle transport across cell compartments is critical for cell function, as in morphologically complex neurons. Specialized cells can undergo programmed elimination, an essential facet of normal development. My central thesis question asks how intracellular transport of mitochondria, the cell’s energy producers, regulate fated elimination of complex cells. I explored this using the specialized tail-spike cell (TSC) of the roundworm C. elegans. The TSC dies embryonically through the novel ‘tripartite’ developmental killing program, Compartmentalized Cell Elimination (CCE).  In my study, I defined and characterized events at the CCE initiation compartment of the TSC. Using transgenic sensors, I discovered local caspase protease activity and Ca²⁺ spikes at the CCE initiation site. I described two novel mitochondrial transport mechanisms involving conserved microtubule motors critical for CCE. I found that, unlike in neurons, the Kinesin-1 homolog transports mitochondria soma-ward and is needed for compartment-specific elimination. Unexpectedly, I found that the Kinesin-3 homolog, classically known for vesicle transport, carries mitochondria out of the TSC soma, and is negatively regulated by caspase. Interestingly, in absence of caspase, mitochondria are transported to the CCE initiation site via Kinesin-3, and prevent CCE initiation. Surprisingly, this local protective role of mitochondria is not by energy production, but rather local Ca²⁺ uptake via the uniporter MCU-1. Intriguingly, in absence of caspase, CCE does begin, but is reversed. Finally, I described region-specific polarity differences in the microtubule cytoskeleton. Together, my thesis work offers new insights into the molecular mechanism and local control of complex cell elimination, with broader implications to cellular resilience.

Disciplines

Cell Biology

License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Sharmin, Rashna, "Mitochondria in Local Control of Programmed Cell Killing & Resilience" (2026). Biology Dissertations-Archive. 232.
https://mavmatrix.uta.edu/biology_dissertations/232