Date Approved
6-16-2026
Embargo Period
6-16-2026
Document Type
Dissertation
Degree Name
Ph.D. Molecular Cell Biology & Neuroscience
Department
Cell and Molecular Biology
College
Rowan-Virtua School of Translational Biomedical Engineering & Sciences
Advisor
Randy Strich, Ph.D.
Committee Member 1
Dmitriy Markov, Ph.D.
Committee Member 2
Katrina Cooper, Ph.D.
Committee Member 3
Kleiton Silva, Ph.D.
Committee Member 4
Francis Luca, Ph.D.
Keywords
Cell Death;Cnc1;Dnm1;Por1;Rho5
Disciplines
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Molecular Biology
Abstract
Regulated cell death is a conserved process with major implications for health and disease, yet how yeast cells integrate stress signals to determine survival versus death remains unclear. This thesis investigates Cyclin C (Cnc1), a conserved Mediator kinase module component with both transcriptional and mitochondrial roles. Together with Cdk8 Cnc1 primarily represses stress response genes, while upon stress it translocates to the mitochondria to induce mitochondrial fragmentation with the dynamin-related GTPase Dnm1. Using structure-guided separation-of-function mutants, I demonstrate that Cnc1-dependent death requires its mitochondrial function rather than its transcriptional role, and that its effector Dnm1 acts as a signaling node rather than a mechanical driver of fission. Extending this framework, I identify a multi-organelle death complex in which the stress-activated Rho GTPase Rho5 and the ER-Mitochondrial encounter structure (ERMES), act downstream of Cnc1-Dnm1 at mitochondrial contact sites, where the Cnc1-Dnm1 module propagates Rho5 pro-death signaling to promote calcium accumulation, vacuolar membrane permeabilization (VMP), and subsequent lethal mitochondrial dysfunction. Temporal and genetic analyses indicate that VMP precedes and is required for mitochondrial dysfunction, defining a Cnc1-Dnm1-Rho5 axis that coordinates mitochondrial and vacuolar disruption to govern stress-induced cell death.
Recommended Citation
Bauer, Justin, "A RHO5-CNC1-DNM1 SIGNALLING MODULE COORDINATES MULTI-ORGANELLE EXECUTION OF REGULATED CELL DEATH IN YEAST" (2026). Theses and Dissertations. 3536.
https://rdw.rowan.edu/etd/3536
