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Mechanisms Regulating Mitochondrial Transfer in Human Corneal Epithelial Cells
Sonali Pal-Ghosh1, Beverly A Karpinski1, Himani Datta-Majumdar1
1Department of Anatomy and Cell Biology, GW School of Medicine and Health Sciences, Washington, District of Columbia, United States.
Investigative Ophthalmology & Visual Science
|November 6, 2024
Summary
Mitochondrial transfer between corneal cells is crucial for homeostasis. Inhibiting Rho-associated kinase (ROCK) and phagocytosis, alongside acid stress, enhances this transfer, vital for corneal health.
Area of Science:
- Ophthalmology
- Cell Biology
- Neuroscience
Background:
- Intraepithelial corneal nerves (ICNs) are vital for corneal epithelial cell homeostasis.
- Rho-associated kinase (ROCK) inhibitors (RIs) influence neuron survival and mitochondrial transfer in corneal cells.
Purpose of the Study:
- To investigate the mechanisms of intercellular mitochondrial transfer in human corneal limbal epithelial (HCLE) cells.
- To assess the impact of cell stress and specific inhibitors on mitochondrial transfer dynamics.
Main Methods:
- Utilized Mitotracker and AAV1 mitotag eGFPmCherry for tracking mitochondrial transfer in HCLE cells and co-cultures with neurons.
- Developed a mitochondrial transfer assay to quantify effects of cell stress, phagocytosis, gap junction, and ROCK inhibition.
Main Results:
- Observed bidirectional mitochondrial transfer between HCLE cells and neurons.
- Mitochondrial transfer in HCLE cells was inhibited by reduced gap junction function but enhanced by acid stress, phagocytosis inhibition, or ROCK inhibition.
- Media from RI-treated cells promoted cell adhesion and mitochondrial transfer.
Conclusions:
- Maximal mitochondrial transfer occurs with functional gap junctions, inhibited ROCK and phagocytosis, and acid stress.
- Reduced mitochondrial content in HCLE cells increases intercellular mitochondrial transfer.
- ROCK inhibition facilitates mitochondrial release and uptake by migrating HCLE cells and neuronal growth cones.
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