Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death
Summary: Cell death is a fundamental aspect of development, homeostasis, and disease; yet, our understanding of non-apoptotic forms of cell death is limited. One such form is phagoptosis, in which one cell utilizes phagocytosis machinery to kill another cell that would otherwise continue living. We...
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doaj-c634fcd04996457e92c49720f2b815052020-11-25T01:15:26ZengElsevierCell Reports2211-12472019-04-012711119.e3Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell DeathAlbert A. Mondragon0Alla Yalonetskaya1Anthony J. Ortega2Yuanhang Zhang3Oandy Naranjo4Johnny Elguero5Won-Suk Chung6Kimberly McCall7Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA; Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biological Sciences, KAIST, Daejeon, South KoreaDepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA; Corresponding authorSummary: Cell death is a fundamental aspect of development, homeostasis, and disease; yet, our understanding of non-apoptotic forms of cell death is limited. One such form is phagoptosis, in which one cell utilizes phagocytosis machinery to kill another cell that would otherwise continue living. We have previously identified a non-autonomous requirement of phagocytosis machinery for the developmental programmed cell death of germline nurse cells in the Drosophila ovary; however, the precise mechanism of death remained elusive. Here, we show that lysosomal machinery acting in epithelial follicle cells is used to non-autonomously induce the death of nearby germline cells. Stretch follicle cells recruit V-ATPases and chloride channels to their plasma membrane to extracellularly acidify the germline and release cathepsins that destroy the nurse cells. Our results reveal a role for lysosomal machinery acting at the plasma membrane to cause the death of neighboring cells, providing insight into mechanisms driving non-autonomous cell death. : Mondragon et al. show that V-ATPase proton pumps localize to the plasma membrane of follicle cells and promote extracellular acidification to eliminate adjacent nurse cells in the Drosophila ovary. The follicle cells subsequently release cathepsins by exocytosis into the nurse cells to promote their final degradation. Keywords: cell death, ovary, phagocytosis, V-ATPase, cathepsin, Drosophila, oogenesis, phagoptosishttp://www.sciencedirect.com/science/article/pii/S221112471930350X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Albert A. Mondragon Alla Yalonetskaya Anthony J. Ortega Yuanhang Zhang Oandy Naranjo Johnny Elguero Won-Suk Chung Kimberly McCall |
spellingShingle |
Albert A. Mondragon Alla Yalonetskaya Anthony J. Ortega Yuanhang Zhang Oandy Naranjo Johnny Elguero Won-Suk Chung Kimberly McCall Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death Cell Reports |
author_facet |
Albert A. Mondragon Alla Yalonetskaya Anthony J. Ortega Yuanhang Zhang Oandy Naranjo Johnny Elguero Won-Suk Chung Kimberly McCall |
author_sort |
Albert A. Mondragon |
title |
Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death |
title_short |
Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death |
title_full |
Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death |
title_fullStr |
Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death |
title_full_unstemmed |
Lysosomal Machinery Drives Extracellular Acidification to Direct Non-apoptotic Cell Death |
title_sort |
lysosomal machinery drives extracellular acidification to direct non-apoptotic cell death |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-04-01 |
description |
Summary: Cell death is a fundamental aspect of development, homeostasis, and disease; yet, our understanding of non-apoptotic forms of cell death is limited. One such form is phagoptosis, in which one cell utilizes phagocytosis machinery to kill another cell that would otherwise continue living. We have previously identified a non-autonomous requirement of phagocytosis machinery for the developmental programmed cell death of germline nurse cells in the Drosophila ovary; however, the precise mechanism of death remained elusive. Here, we show that lysosomal machinery acting in epithelial follicle cells is used to non-autonomously induce the death of nearby germline cells. Stretch follicle cells recruit V-ATPases and chloride channels to their plasma membrane to extracellularly acidify the germline and release cathepsins that destroy the nurse cells. Our results reveal a role for lysosomal machinery acting at the plasma membrane to cause the death of neighboring cells, providing insight into mechanisms driving non-autonomous cell death. : Mondragon et al. show that V-ATPase proton pumps localize to the plasma membrane of follicle cells and promote extracellular acidification to eliminate adjacent nurse cells in the Drosophila ovary. The follicle cells subsequently release cathepsins by exocytosis into the nurse cells to promote their final degradation. Keywords: cell death, ovary, phagocytosis, V-ATPase, cathepsin, Drosophila, oogenesis, phagoptosis |
url |
http://www.sciencedirect.com/science/article/pii/S221112471930350X |
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