Publication Date
7-1-2024
Document Type
Article
Publication Title
Molecular Biology of the Cell
Volume
35
Issue
7
DOI
10.1091/mbc.E24-02-0058
Abstract
Autophagy is a conserved catabolic process where double membrane-bound structures form around macromolecules or organelles targeted for degradation. Autophagosomes fuse with lysosomes to facilitate degradation and macromolecule recycling for homeostasis or growth in a cell autonomous manner. In cancer cells, autophagy is often up-regulated and helps cancer cells survive nutrient deprivation and stressful growth conditions. Here, we propose that the increased intracellular pH (pHi) common to cancer cells is sufficient to induce autophagic cell death. We previously developed tools to increase pHi in the Drosophila eye via overexpression of DNhe2, resulting in aberrant patterning and reduced tissue size. We examined fly eyes at earlier stages of development and found fewer interommatidial cells. We next tested whether this decrease in cell number was due to increased cell death. We found that the DNhe2-induced cell death was caspase independent, which is inconsistent with apoptosis. However, this cell death required autophagy genes, which supports autophagy as the mode of cell death. We also found that expression of molecular markers supports increased autophagy. Together, our findings suggest new roles for ion transport proteins in regulating conserved, critical developmental processes and provide evidence for new paradigms in growth control.
Funding Number
SC3GM132049
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Department
Biological Sciences
Recommended Citation
Jobelle Peralta, Blake DuPriest, Daniel Orozco, Juan Reyna Pacheco, Laura Martins, Rachel Ann Soriano, Alan Wong, Ramy Wong, and Bree Grillo-Hill. "Drosophila Nhe2 overexpression induces autophagic cell death" Molecular Biology of the Cell (2024). https://doi.org/10.1091/mbc.E24-02-0058
