Autophagic cell death
Beyond apoptosis and regulated necrosis, autophagic cell death is receiving attention as an interesting third form of PCD. Autophagy is in fact, an adaptive mechanism essential for cell survival under unfavorable conditions such as starvation, extracellular or intracellular stress, high temperatures, overcrowding, hypoxia and antiproliferative stimuli (reviewed in (He & Klionsky, 2009)). During the autophagic mechanism, the cell orchestrates a complex response that includes different membrane rearrangements to form autophagosomes and ultimately autolysosomes, allowing the cell to digest and catabolize its own constituents to obtain energy and recycle intracellular molecules (He & Klionsky, 2009). However, this process can lead eventually to a form of cell death, in which the cell “eat itself”, causing irreversible damage like loss of membrane and organelle integrity (Gudipaty et al., 2018; Tsujimoto & Shimizu, 2005). Therefore, autophagy is tightly regulated and depends on a sequence of specific intracellular events. This multistep process is mediated by a gene family termed as ATG (autophagy-related genes) and involves protein-protein interactions and posttranslational modifications, such as the lipidation of the microtubule-binding protein LC3 (light chain 3) with phosphatidylethanolamine and the degradation of p62 (reviewed in (Yang et al., 2015)). Autophagy is a classic pathway that has been studied for years, but more recently, autophagic cell death is getting attention as a defensive and regulatory mechanism rather than a deregulation of the process (D’Arcy, 2019; Yonekawa & Thorburn, 2013). According to this, autophagic cell death can acts in a similar way to apoptosis or necroptosis, representing another self-induced type of cell death in response to extracellular stressors or pathological stimuli.