Role of the inositol 1,4,5-trisphosphate receptor/Ca²⁺-release channel in autophagy

• Main Authors: Parys Jan B, Decuypere Jean-Paul, Bultynck Geert
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: Cell Communication and Signaling
• Subjects: Ca²⁺; Autophagy; Inositol 1,4,5-trisphosphate receptor; Beclin 1; Bcl-2; AMP-activated kinase; Mammalian target of rapamycin; Calmodulin-dependent kinase kinase β
• Online Access: http://www.biosignaling.com/content/10/1/17

<p>Abstract</p> <p>Autophagy is an important cell-biological process responsible for the disposal of long-lived proteins, protein aggregates, defective organelles and intracellular pathogens. It is activated in response to cellular stress and plays a role in development, cell differentiation, and ageing. Moreover, it has been shown to be involved in different pathologies, including cancer and neurodegenerative diseases. It is a long standing issue whether and how the Ca²⁺ ion is involved in its regulation. The role of the inositol 1,4,5-trisphosphate receptor, the main intracellular Ca²⁺-release channel, in apoptosis is well recognized, but its role in autophagy only recently emerged and is therefore much less well understood. Positive as well as negative effects on autophagy have been reported for both the inositol 1,4,5-trisphosphate receptor and Ca²⁺. This review will critically present the evidence for a role of the inositol 1,4,5-trisphosphate receptor/Ca²⁺-release channel in autophagy and will demonstrate that depending on the cellular conditions it can either suppress or promote autophagy. Suppression occurs through Ca²⁺ signals directed to the mitochondria, fueling ATP production and decreasing AMP-activated kinase activity. In contrast, Ca²⁺-induced autophagy can be mediated by several pathways including calmodulin-dependent kinase kinase β, calmodulin-dependent kinase I, protein kinase C θ, and/or extracellular signal-regulated kinase.</p>