Abstract
In the last few years, metabolism has been shown to be controlled by cross-organelle communication. The relationship between the endoplasmic reticulum and mitochondria/lysosomes is the most studied; here, inositol 1,4,5-triphosphate (IP3) receptor (IP3R)-mediated calcium (Ca2+) release plays a central role. Recent evidence suggests that IP3R isoforms participate in synthesis and degradation pathways. This minireview will summarize the current findings in this area, emphasizing the critical role of Ca2+ communication on organelle function as well as catabolism and anabolism, particularly in cancer.
Highlights
The life of a cell appears as an entanglement of complex networks of synthesis and degradation of molecules in a dynamic equilibrium essential for its viability (Muchowska et al, 2020)
Xestospongin B (XeB), an alkaloid obtained from the marine sponge Xestospongia exigua, inhibits IP3R-mediated Ca2+ release (Jaimovich et al, 2005), selectively inducing nonapoptotic cell death of some types of cancer cells (Cárdenas et al, 2017; Cardenas et al, 2020)
Ca2+ flux interruption leads cancer cells into a metabolic and bioenergetic crisis that ends in cell death (Silva-Pavez et al, 2020)
Summary
The life of a cell appears as an entanglement of complex networks of synthesis and degradation of molecules in a dynamic equilibrium essential for its viability (Muchowska et al, 2020). Autophagy can be regulated by the release of lysosomal Ca2+ stores to cytoplasm, inducing the activity of calcineurin, a Ca2+-dependent phosphatase, which dephosphorylates the transcription factor EB (TFEB) and allows its translocation to the nucleus (Medina et al, 2015; Figure 1B). TFEB is a master regulator of the coordinated lysosomal expression and regulation (CLEAR) network, a gene network associated with the lysosome and autophagy (Palmieri et al, 2011) Another interesting fact described by Cang et al (2013) pertains to the role of two pore channels (TPCs) on cellular metabolism. Peng et al (2020) have described the occurrence of Ca2+ fluxes between lysosomes and mitochondria, via the lysosomal ion channel MCOLN1 and the mitochondrial transporter VDAC (Figure 1B) Such a discovery opened a new path to target Ca2+ regulation of mitochondrial metabolism for therapeutic purposes. The relationships between Ca2+ and lipids associated to lysosomes have been shown before (Van Der Kant and Neefjes, 2014); it is still unclear if IP3R Ca2+ release is involved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
