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.