Role of inositol polyphosphates in programed cell death in Dictyostelium discoideum and its developmental life cycle

Abstract

Programed cell death or apoptosis is a key developmental process that maintains tissue homeostasis in multicellular organisms. Inositol polyphosphates (InsPs) are key signaling molecules known to regulate a variety of cellular processes including apoptosis in such organisms. The signaling role of InsPs in unicellular organisms such as Dictyostelium discoideum (D. discoideum) is not well understood. We investigated whether InsPs also play any role in apoptosis in D. discoideum and whether InsPs-mediated apoptosis follows a mechanism similar to that present in higher multicellular eukaryotes. We measured known apoptotic markers in response to exogenously administered InsP, the major InsPs in the cell. We found that InsP was able to cause cell death in D. discoideum cell culture in a dose- and time-dependent manner as determined by cytotoxicity assays. Fluorescence staining with acridine orange/ethidium bromide and flow cytometry results confirmed that the cell death in D. discoideum by InsP was due to apoptotic changes. Poly(ADP-ribose) expression, a known apoptotic marker used in D. discoideum, was also increased following InsP treatment suggesting a role for InsP-mediated apoptosis in this organism. InsP-mediated cell death was accompanied by production of reactive oxygen species and a decrease in mitochondrial membrane potential. Additionally, we studied the effects of InsP on the developmental life cycle of D. discoideum, the process likely affected by apoptosis. In conclusion, our studies provide evidence that InsP-mediated cell death process is conserved in D. discoideum and plays an important signaling role in its developmental life cycle.

The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis

“…At the start of the new millennium, the social amoeba was used to study the effect on the inositol phosphate metabolism of lithium and other mood stabilizing drugs ( King et al, 2010 ; Williams et al, 1999 , 2002 ). More recently, D. discoideum was used to characterise the roles of inositol polyphosphate in programmed cell death ( Al-Anbaky et al, 2018 ) and to characterise the phytocannabinoid-dependent mTORC1 regulation by the inositol polyphosphate multikinase ( Damstra-Oddy et al, 2021 ). However, the precise description of the inositol phosphate metabolic pathway and the characterization of the different inositol kinase mutants is still missing in the amoeba.…”

Selenium protects against cadmium‐induced cardiac injury by attenuating programmed cell death viaPI3K/AKT/PTENsignaling

“…Programmed cell death is one of the most important forms of cell death that is regulated by a variety of genes or signal transduction pathways 20 . In recent years, its mechanism has become the focus of research in the field of life science and medicine, especially pyroptosis, autophagy, and apoptosis, which are the three most common types of programmed cell death in the body 21 .…”

“…Programmed cell death is one of the most important forms of cell death that is regulated by a variety of genes or signal transduction pathways. 20 In recent years, its mechanism has become the focus of research in the field of life science and medicine, especially pyroptosis, autophagy, and apoptosis, which are the three most common types of programmed cell death in the body. 21 Different from autophagy and apoptosis, pyroptosis is characterized by the caspase-1-mediated rapid cell death which depends on the activation of inflammasomes to promote inflammation.…”