Metabolic regulation of the PMCA: Role in cell death and survival

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The plasma membrane Ca2+-ATPase (PMCA) is a ubiquitously expressed, ATP-driven Ca2+
pump that is critical for maintaining low resting cytosolic Ca2+ ([Ca2+]i) in all eukaryotic cells.
Since cytotoxic Ca2+ overload has such a central role in cell death, the PMCA represents an
essential “linchpin” for the delicate balance between cell survival and cell death. In general,
impaired PMCA activity and reduced PMCA expression leads to cytotoxic Ca2+ overload and
Ca2+ dependent cell death, both apoptosis and necrosis, whereas maintenance of PMCA
activity or PMCA overexpression is generally accepted as being cytoprotective. However, the
PMCA has a paradoxical role in cell death depending on the cell type and cellular context. The
PMCA can be differentially regulated by Ca2+-dependent proteolysis, can be maintained by a
localised glycolytic ATP supply, even in the face of global ATP depletion, and can be
profoundly affected by the specific phospholipid environment that it sits within the membrane.
The major focus of this review is to highlight some of the controversies surrounding the
paradoxical role of the PMCA in cell death and survival, challenging the conventional view of
ATP-dependent regulation of the PMCA and how this might influence cell fate.
Original languageEnglish
JournalCell calcium
Early online date8 Jun 2017
Publication statusPublished - 2017

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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