Theses and Dissertations

Date of Award

5-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Robert Gilkerson

Second Advisor

Dr. Megan Keniry

Third Advisor

Dr. Michael Persans

Abstract

Mitochondria are eukaryotic cellular organelles that play a role in energy production, apoptosis, integrated stress response, and aging. Mitochondrial dynamics is the physical fusion (interconnection) and fission (fragmentation) of mitochondria within a cell and tightly regulates mitochondrial functions. Optic atrophy 1 (OPA1) is a dynamin-related GTPase located in the inner mitochondrial membrane, and is responsible for inner mitochondrial membrane fusion. OPA1 exists in five isoforms, the two fusion-active long OPA1 (L-OPA1) and the three fusion-inactive short OPA1 (S-OPA1) isoforms. When the transmembrane potential (∆ψm) is aggravated, the inner membrane metalloprotease OMA1 is activated, causing the complete cleavage of L-OPA1 to S-OPA1. Absence of L-OPA1 results in mitochondrial fragmentation, impairing mitochondrial function and negatively impacting the cell. Our research explores OMA1-mediated OPA1 processing after disruption of the ∆ψm via carbonyl cyanide 3-chlorophenyl hydrazine (CCCP) challenge in H9c2 and L6.C11 myoblasts before and after differentiation with all-trans-retinoic acid. Further, we investigate the recapitulation of OPA1 processing after the inhibition of mitochondrial ribosomes via chloramphenicol (CAP). Interestingly, OPA1 processing after CCCP challenge is absent in H9c2 and L6.C11 myoblasts but is robustly activated after differentiation. Additionally, OPA1 processing in myoblasts is rescued after CAP treatment. These findings suggest the possibility of a developmental OPA1 processing switch regulating OMA1 activity.

Comments

Copyright 2023 Omar Agustin Carrillo. All Rights Reserved.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/dissertations-theses/activation-opa1-processing-differentiated/docview/2842683829/se-2?accountid=7119

Available for download on Friday, July 25, 2025

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