Parthanatos

Parthanatos (derived from the Greek Θάνατος, "Death") is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria. Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIF. Parthanatos is involved in diseases that afflict hundreds of millions of people worldwide. Well known diseases involving parthanatos include Parkinson's disease, stroke, heart attack, and diabetes. It also has potential use as a treatment for ameliorating disease and various medical conditions such as diabetes and obesity. The term parthanatos was not coined until a review in 2009. The word parthanatos is derived from Thanatos, the personification of death in Greek mythology. Parthanatos was first discovered in a 2006 paper by Yu et al. studying the increased production of mitochondrial reactive oxygen species (ROS) by hyperglycemia. This phenomenon is linked with negative effects arising from clinical complications of diabetes and obesity. Researchers noticed that high glucose concentrations led to overproduction of reactive oxygen species and rapid fragmentation of mitochondria. Inhibition of mitochondrial pyruvate uptake blocked the increase of ROS, but did not prevent mitochondrial fragmentation. After incubating cells with the non-metabolizable stereoisomer L-glucose, neither reactive oxygen species increase nor mitochondrial fragmentation were observed. Ultimately, the researchers found that mitochondrial fragmentation mediated by the fission process is a necessary component for high glucose-induced respiration increase and ROS overproduction.