Date of Award
Master of Science (MS)
Biochemistry and Molecular Biology
Dr. Robert Gilkerson
Dr. Hassan Ahmad
Dr. Saraswathy Nair
Mitochondria is an energy-producing organelle in the cell that accept electrons from the Krebs cycle to generate energy in the form of ATP by oxidative phosphorylation. Two mitochondrial aspects, bioenergetics and dynamics are critical for energy balance and cellular stress responses. Mitochondrial dynamics refers to the balance between mitochondrial fusion (mitochondrial biogenesis) and mitochondrial fission (mitochondrial fragmentation). Cellular stress conditions that lead to dissipation of transmembrane potential (Δψm) trigger the activation of an IMM protein, OMA1, a metalloprotease that leads to processing of another IMM protein, optic atrophy-1 (OPA1) that mediates IMM fusion. Persistent stress primes the mitochondria to mitophagy and the cell to cell-wide mechanisms such as apoptosis and integrated stress response. However, our data demonstrates that undifferentiated myoblast cells are unresponsive to change in Δψm but that OMA1 activation and OPA1 processing is restored along with increased apoptotic sensitivity after differentiating the cells into cardiomyocytes and skeletal muscle cells indicating towards a potential ‘developmental switch’. Moreover, undifferentiated myoblasts also become stress-responsive upon inhibiting mitochondrial protein synthesis. We also found that L-OPA1 is required to mediate myoblast differentiation as well as ‘switch’ activation. These findings suggest that ‘clutch’ activation potentiates a novel mechanism of OMA1 activation.
Kaur, Harpreet, "Understanding the Developmental Regulation of OPA1 Processing in C2C12 Myoblasts" (2023). Theses and Dissertations. 1231.
Available for download on Friday, July 25, 2025