Involvement of poly(ADP-ribose) polymerase in paraptotic cell death of D. discoideum.

Paraptosis is mediated by several proteins, poly(ADP-ribose) polymerase being one of them. D. discoideum lacks caspases thus providing a better system to dissect out the role of in paraptosis. The cell death phenotype in unicellular eukaryote, D. discoideum is similar to the programmed cell death phenotype of multicellular animals. However, the events downstream to the death signal of PCD in D. discoideum are yet to be understood. Our results emphasize that oxidative stress in D. discoideum lacking caspases leads to Pduanyu37 activation, mitochondrial membrane potential changes, followed by the release of apoptosis inducing factor from mitochondria. AIF causes large scale DNA fragmentation, a hallmark feature of paraptosis. The role of Pduanyu37 in paraptosis is reiterated via Pduanyu37 inhibition by benzamide, PARG inhibition by gallotannin and Pduanyu37 down-regulation, which delays paraptosis. PARG and AIF interplay is quintessential in paraptosis of D. discoideum. This is the first report to establish the involvement of Pduanyu37 in the absence of caspase activity in D. discoideum which could be of evolutionary significance and gives a lead to understand the caspase independent paraptotic mechanism in higher organisms.

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