**7. Parp proteolysis as an indicator of cell death**

Poly-ADP-Ribose Polymerase (PARP) is a family of 16 nuclear enzymes, among which, the best characterized is PARP-1. PARPs have several functions in cell proliferation, cell death, DNA recombination and DNA repair. PARP-1 is a 116 kDa nuclear protein involved in DNA repair mechanisms. PARP synthesis is activated when DNA is fragmented in the presence of nuclear poly-ADP ribosylated proteins. In an early apoptotic stage, caspases cleave PARP resulting in an 89 kDa and a 24 kDa fragments [73]. The smaller fragment irreversibly binds DNA fragment ends, impeding the access of DNA repair enzymes. Hence, PARP proteolysis facilitates nuclear disorganization and ensures irreversibility of the apoptotic process [74]. PARP cleaves also takes place during necrosis. However, the fragments obtained are of different size [75]. A role of PARP cleavage in autophagy induced by DNA damage has been recently suggested [76]. **Parthanatos** is a particular case of regulated necrosis in which PARP activation plays an important role. PAR polymer, the product of PARP-1 activation, translocates to the mitochondria and induces AIF release. Subsequently, AIF translocates to the nucleus and provokes chromatin condensation and DNA fragmentation [77]. Necroptosis or regulated necrosis also involves PARP activation [78]. Therefore, PARP can participate in different types of cell death and it is not exclusive of apoptosis, as previously thought.
