Dissertation Defense: Differential expression of the mitochondrial calcium uniporter (MCU) in hippocampal neurons attunes mitochondrial calcium handling and bioenergetics
Dissertation Defense: Differential Expression of the Mitochondrial Calcium Uniporter (MCU) in Hippocampal Neurons Attunes Mitochondrial Calcium Handling and Bioenergetics
Mikel L. Cawley
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Farris Lab, Fralin Biomedical Research Institute at VTC
April 22, 2026, at 2 p.m.
Room M106, 2 Riverside Circle
About this Dissertation
Mitochondria are precisely positioned throughout neuronal axons and dendrites to meet unique energy demands across functionally distinct compartments. Dendritic mitochondria can be molecularly, structurally, and functionally distinct depending on the neuron type, supporting the diversity of synaptic functions and connectivity patterns across brain areas. A better understanding of how heterogeneous properties, such as mitochondrial morphology, dynamics, and function, converge to support cell- and compartment-specific metabolic demands, is crucial for elucidating how mitochondrial heterogeneity affects intact circuits. We found that the mitochondrial calcium uniporter (MCU) is endogenously enriched in the distal apical dendrites of CA2, precisely where CA2 neurons receive entorhinal cortical inputs carrying social information. Mitochondrial calcium uptake is tightly coupled to neuronal activity and stimulates the TCA cycle by activating calcium-dependent enzymes important for oxidative phosphorylation. Given the substantial energetic demand on neuronal mitochondria, Cawley, mentored by Shannon Farris, hypothesized that the enrichment of MCU in distal dendrites indicated mitochondria with a greater capacity to meet energy demand. However, the functional significance of expressing more MCU remained unclear. To determine whether mitochondria enriched with MCU exhibited enhanced bioenergetic properties, Cawley tested whether MCU overexpression increased the capacity for mitochondrial calcium buffering and oxidative phosphorylation. She reports enhanced mitochondrial calcium uptake rates in hippocampal mitochondria overexpressing MCU without increased sensitivity to calcium overload. Moreover, Cawley's research revealed that the efficiency of mitochondrial respiration scales proportionally with bioenergetic demand. These findings suggest that differential expression of MCU can modulate mitochondrial calcium uptake and respiration under increasing demand and expand our understanding of how mitochondrial heterogeneity supports neuronal function and may be critical for understanding cell-type-specific vulnerability to mitochondrial dysfunction in the brain.
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Northern Michigan University, M.S., Biology
Northern Michigan University, B.S., Biology
Training
Graduate Research Assistant, Farris Lab, Fralin Biomedical Research Institute at VTC
Mentor
Shannon Farris, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
Committee Members
- Michael Fox, Ph.D., Dean, College of Natural Sciences, University of Massachusetts, Amherst
- Jessica Pfleger-Karch.D., Assistant Professor, Baylor College of Medicine
- Zhen Yan, Ph.D., Professor and Director, Center for Exercise Medicine Research, Fralin Biomedical Research Institute at VTC
Publications
Cawley, M.L. et al. (2026) “Elevating levels of neuronal MCU in the hippocampus enhances mitochondrial calcium uptake and respiratory efficiency proportional to demand,” bioRxiv, p. 2026.04.13.718264. Available at: https://doi.org/10.64898/2026.04.13.718264.
Cawley, M.L., Farris, S., 2026. The impact of dendritic mitochondrial heterogeneity on synapse function. Trends Neurosci. S0166-2236(26)00014–7. https://doi.org/10.1016/j.tins.2026.01.011
Pannoni, K.E., Fischer, Q.S., Tarannum, R., Cawley, M.L., Alsalman, M.M., Acosta, N., Ezigbo, C., Gil, D.V., Campbell, L.A., Farris, S., 2025. MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity. Sci. Rep. 15, 4540. https://doi.org/10.1038/s41598-025-85958-4
Pannoni, K.E., Gil, D., Cawley, M.L., Alsalman, M.M., Campbell, L.A., Farris, S., 2023. Layer-specific mitochondrial diversity across hippocampal CA2 dendrites. Hippocampus 33, 182–196. https://doi.org/10.1002/hipo.23512
Carrillo, G.L., Su, J., Cawley, M.L., Wei, D., Gill, S.K., Blader, I.J., Fox, M.A., 2023. Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection. J. Neurochem. https://doi.org/10.1111/jnc.15770
Shin, S., You, I.-J., Jeong, M., Bae, Y., Wang, X.-Y., Cawley, M.L., Han, A., Lim, B.K., 2023. Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus-brainstem pathway. Nat. Neurosci. 26, 79–91. https://doi.org/10.1038/s41593-022-01208-0Presentations
Posters
International
Mikel L. Cawley, Ryan N. Montalvo, Mason Wheeler, Zhen Yan, Shannon Farris. Elevating MCU levels in the hippocampus increases mitochondrial calcium uptake and respiration. Gordon Research Seminar: Mitochondria in Health and Disease. (2025) Bi-annual Meeting, Ventura Beach, CA.
Mikel L. Cawley, Ryan N. Montalvo, Mason Wheeler, Zhen Yan, Shannon Farris. Elevating MCU levels in the hippocampus increases mitochondrial calcium uptake and respiration. Gordon Research Conference: Mitochondria Metabolism and Signaling. (2025) Bi-annual Meeting, Ventura Beach, CA.
Mikel L. Cawley, Ryan N. Montalvo, Mason Wheeler, Zhen Yan, Shannon Farris. Elevating neuronal MCU levels in the hippocampus increases mitochondrial calcium uptake and respiration. Society for Neuroscience. (2024) Annual Meeting, Chicago, IL.
Regional/Internal
Mikel L. Cawley, Ryan Montalvo, Mayd Alsalman, Daniel W. Creighton, Renesa Tarannum, Katy Pannoni, Shannon Farris. Investigating the role of MCU in powering circuit-specific forms of structural plasticity. Central Virginia Chapter of the Society for Neuroscience. (2024) Annual Meeting, Blacksburg, VA.
Mikel L. Cawley, Mayd Alsalman, Daniel W. Creighton, Renesa Tarannum, Katy Pannoni, Shannon Farris. Investigating the role of MCU in powering circuit-specific forms of structural plasticity. Translational Biology Medicine and Health Winter Symposium. (2023) Annual Meeting, Roanoke, VA.
Mikel L. Cawley, Katy Pannoni, Mayd Alsalman, Shannon Farris. Investigating a role for MCU expression in the support of mitochondrial heterogeneity and circuit-specific bioenergetics. Center for Neurobiology Research Symposium. (2023) Annual Meeting, Roanoke, VA.
Mikel L. Cawley, Katy Pannoni, Mayd Alsalman, Shannon Farris. Investigating a role for MCU expression in the support of mitochondrial heterogeneity and circuit-specific bioenergetics. Advancing Neuroscience Research Symposium. (2023) Annual Meeting, Roanoke, VA.
Mikel L. Cawley, Katy Pannoni, Mayd Alsalman, Shannon Farris. Mitochondrial Diversity Across Hippocampal Dendrites. Translational Biology Medicine and Health Winter Symposium. (2023) Annual Meeting, Roanoke, VA. *Awarded First Place*
Mikel L. Cawley, In-Jee You, Sora Shin. Proenkephalin-expression neurons of the hypothalamus mediate stress-induced overconsumption of palatable foods. Translational Research Experience: TBMH Poster Session. (2022) Life Sciences at Virginia Tech, Blacksburg, VA.
Oral Presentations
Mikel L. Cawley. (2025). Elevating MCU levels in the hippocampus increases mitochondrial calcium uptake and respiration. Research in Progress Symposium. (2025) Fralin Biomedical Research Institute at VTC, Roanoke, VA.
Mikel L. Cawley. (2024). Mitochondrial Diversity in the Hippocampus. Center for Neurobiology Research Symposium. Annual meeting, Roanoke, VA
Mikel L. Cawley. (2024). Circuit-Specific Mitochondrial Diversity in the Hippocampus. Podium Talk at the Fralin Biomedical Research Institute Retreat. Annual Retreat, Omni Homestead Resort, VA.
Mikel L. Cawley. (2023). Investigating the Role of MCU in Powering Circuit-specific Forms of Structural Plasticity. Research in Progress Symposium. Fralin Biomedical Research Institute at VTC, Roanoke, VA.
Mikel L. Cawley. (2022). Rotation 3 Oral Presentation: Lab of Dr. Shannon Farris. Translational Research Experience (2022) Fralin Biomedical Research Institute, Roanoke, VA.
Mikel L. Cawley, Mary Frazier, Collin Gregg, Suen Imani, Mona Safari. (2021). illuminostics: illuminating the path to care. Health Sciences and Technology Hokie Pitch. Fralin Biomedical Research Institute at VTC, Roanoke, VA. *Awarded First Place*
- Selected Young Scientist to present at the 2025 Mitochondria in Health & Disease Gordon Research Seminar, a competitive forum for early‑career researchers (2025)
- Certification for Cold Spring Harbor Laboratory, Quantitative Imaging: From Acquisition to Analysis Course (2024)
- Awarded scholarship to attend Cold Spring Harbor Laboratory, Quantitative Imaging: From Acquisition to Analysis Course(2024)
- James R. Carter, Sr., Memorial Award for Translational Neuroscience Research (2024)
- Translational, Biology, Medicine, and Health Student Ambassador Program (2024)
- Student Ambassador for the Blue Ridge Partnership for Health Science Careers (2023)
- Finalist for Translational, Biology, Medicine, and Health Graduate Program Student of the Year in Science (2023)
- 1st Place Poster Presentation Virginia Tech Translational, Biology, Medicine, and Health Winter Symposium (2022)
- Finalist for Translational, Biology, Medicine, and Health Student of the Year in Education
- 1st Place at the Virgnia Tech Health Sciences and Technology Hokie Pitch (2021)
- Health Sciences and Career Advisory Summit - Served on Student Panel as a Blue Ridge Partnership Student Ambassador, Roanoke, VA
- Glenvar High School - Invited speaker for Brain Awareness Week in two AP biology classrooms - Roanoke, VA
- Virginia Western Community College - Served on Graduate Panel for VWCC STEM Outreach