Regulation of autophagy by Ca2+

Abstract

Autophagy is an evolutionarily conserved lysosomal catabolic process used as an internal engine in response to nutrient starvation or metabolic stress. A number of protein complexes and an intricate network of stress signaling cascades impinge on the regulation of autophagy; the mammalian target of rapamycin serves as a canonical player. Ca2+, as a major intracellular second messenger, regulates multiple physiological and pathological functions. Although significant information is already well-established about the role of Ca2+ in apoptosis, its role in autophagy has been recently determined and is poorly understood. Intracellular Ca2+ positively and negatively affects autophagy. In this review, evidence for both views and the interplay of Ca2+ between autophagy and apoptosis induction are discussed. The available data revealed the bidirectional role of Ca2+ in the regulation of autophagy. Moreover, the data also indicated that this role probably depends on the context of time, space, Ca2+ source, and cell state, thus either preventing or enhancing autophagy.

Mechanistic target of rapamycin inhibition with rapamycin induces autophagy and correlative regulation in white shrimp (Litopenaeus vannamei)

“…As described previously, the relationship between autophagy and apoptosis is controversial (Sun, Xu, Wang, & Zhang, ). Under certain conditions, autophagy promotes a stress adaptation (avoiding cell death) and suppresses apoptosis.…”

Aberrant regulation of autophagy in mammalian diseases

“…mTOR phosphorylation can inhibit the autophagic activity of cells, and the mTOR inhibitor rapamycin has been shown to suppress mTOR phosphorylation and thereby activate the autophagic activity. Other signalling pathways regulating autophagy include the Ras/Raf/ERK [12], calcium/calmodulin-dependent protein kinase-II (CaMK-II) [13], and mTOR-independent inositol signalling pathways [14]. Importantly, failure to precisely control these signalling networks involved in regulating autophagic activity can lead to a variety of diseases.…”

Calcium channel blockers and the incidence of breast and prostate cancer: A meta-analysis

“…11 The blockade of calcium entry by pharmacologic means would inhibit this important process and disable the body's natural defence mechanism against cancer growth. 12,13 Calcium channel blockers (CCBs) are used extensively in the treatment of hypertension, ischaemic heart disease and supraventricular arrhythmias. This is an intracellular degradation system which allows the cell to consume defective materials in times of physiologic stress, thus avoiding activation of global cell death.…”

“…these findings in the clinical setting. This is especially true when considering the intracellular effect of verapamil, which uniquely increases microtubule-associated protein 1 light chain 3-II (LC3-II) levels in cell models 12. This indicates the influence of factors related to each study's research methodology as a contributor to the overall summary effect.…”

“…This is an intracellular degradation system which allows the cell to consume defective materials in times of physiologic stress, thus avoiding activation of global cell death. 12,13 Calcium channel blockers (CCBs) are used extensively in the treatment of hypertension, ischaemic heart disease and supraventricular arrhythmias. 14…”