Theses and Dissertations

Date of Award

8-1-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Robert Gilkerson

Second Advisor

Megan Keniry

Third Advisor

Michael Persans

Abstract

Mitochondria play a pivotal role in metabolic energy production, cellular signaling, and apoptosis. To carry out these key cellular roles, mitochondria dynamically balance their organization through opposing including fusion and fission processes. The balance between mitochondrial fusion and fission is regulated by key proteins such as OPA1 (optic atrophy 1) and OMA1 (overlapping activity with metalloprotease). More recently, mitochondria have been increasingly revealed to play key roles in cellular differentiation, where metabolic demands are reprogrammed. This study aims to elucidate the specific roles of OPA1 and OMA1 in the differentiation of C2C12 myoblast cells into myotubes.

Our data demonstrates that differentiation of C2C12 myoblasts with 2% horse serum (HS) causes formation of elongate, multinucleate myotubes, as demonstrated by confocal immunomicroscopy and Western blotting. Moreover, OPA1 genetic knockdown disrupts myogenic differentiation. These findings motivate our hypothesis: OPA1-mediated mitochondrial fusion is required for myogenic differentiation. To test this, we examined whether Mdivi-1 would affect mitochondrial dynamics. Mdivi-1 inhibits mitochondrial fission leaving OPA1-mediated fusion unopposed. Our data suggest that mdivi-1 blunts C2C12 differentiation. Further experiments will directly test whether OPA1 is required for differentiation by genetic knockout.

Comments

Copyright 2025 Daniel Eloy Bazan. All Rights Reserved. https://proquest.com/docview/3275034231

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