Mobilization of lysosomal calcium regulates the externalization of phosphatidylserine during Apoptosis

Banafsheh Mirnikjoo, Krishnakumar Balasubramanina, Alan J. Schroit

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

A hallmark of apoptotic cells is the Ca2+-dependent appearance of phosphatidylserine (PS) at the cell surface as a result of its redistribution from the inner-to-outer plasma membrane leaflet. Although endoplasmic reticulum and mitochondrial Ca2+ are known to participate in apoptosis, their role in PS externalization has not been established. In this study, several organelle-specific fluorescent markers and Ca2+-sensitive probes were used to identify the source of Ca2+ critical to PS externalization. By employing Rhod-2AM, fluorescein-labeled high molecular weight dextran, and Calcium Green 1, we provide evidence that lysosomes respond to apoptotic stimuli by releasing their luminal Ca2+ to the cytosol. Cells treated with the cytosolic phospholipase A2 inhibitor, cPLA2α, had no effect on caspase activation but exhibited a significant decrease in lysosomal Ca2+ release and externalization of PS in response to apoptotic stimuli. Similarly, cells depleted of lysosomal Ca2+ underwent programmed cell death yet failed to externalize PS. These data indicate that although Ca2+ release from other intracellular organelles to the cytosol is adequate for apoptosis, the release of Ca2+ from lysosomes is critical for PS externalization.

Original languageEnglish (US)
Pages (from-to)6918-6923
Number of pages6
JournalJournal of Biological Chemistry
Volume284
Issue number11
DOIs
StatePublished - Mar 13 2009

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Phosphatidylserines
Apoptosis
Calcium
Lysosomes
Organelles
Cytosol
Cell death
Cell membranes
Caspases
Dextrans
Fluorescein
Endoplasmic Reticulum
Cell Death
Molecular Weight
Chemical activation
Molecular weight
Cells
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mobilization of lysosomal calcium regulates the externalization of phosphatidylserine during Apoptosis. / Mirnikjoo, Banafsheh; Balasubramanina, Krishnakumar; Schroit, Alan J.

In: Journal of Biological Chemistry, Vol. 284, No. 11, 13.03.2009, p. 6918-6923.

Research output: Contribution to journalArticle

Mirnikjoo, Banafsheh ; Balasubramanina, Krishnakumar ; Schroit, Alan J. / Mobilization of lysosomal calcium regulates the externalization of phosphatidylserine during Apoptosis. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 11. pp. 6918-6923.
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