Calcium signaling regulates autophagy and apoptosis

Pramod Sukumaran, Viviane Nascimento Da Conceicao, Yuyang Sun, Naseem Ahamad, Luis R. Saraiva, Senthil Selvaraj, Brij B. Singh

Research output: Contribution to journalReview articlepeer-review

Abstract

Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.

Original languageEnglish (US)
Article number2125
JournalCells
Volume10
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Apoptosis
  • Autophagy
  • Calcium channels
  • Calcium signaling
  • Neuronal and immune cell function
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)

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