Cell death pathways in pathogenic trypanosomatids: lessons of (over)kill

After the autophagic induction, phagophore elongates from endoplasmic reticulum or Golgi profiles, engulfing non-functional organelles and molecules. After the elongation step, autophagosome is formed, taking the cargo to be degraded in lysosome. All steps are regulated by Atg proteins. Autophagic cell death occurs when the homeostatic balance is broken by the continuous autophagic induction. In trypanosomatids, apoptosis-like cell death is characterized especially by the effect on the mitochondrion, with loss of its membrane potential, and release of cytochrome c to the cytosol. Among other classical apoptotic phenotypes, DNA fragmentation (derived from EndoG activity) and PS exposure were also described in these protozoa. The participation of metacaspases is still debatable as well as the presence of apoptotic Bcl-2 family regulators. Necrotic pathway is evidenced by the intense cytosolic vacuolization, strong effect on the mitochondrion, randomic DNA fragmentation and plasma membrane disruptio