The cell on the edge of life and death: Crosstalk between autophagy and apoptosis

Abstract

Recently, the crosstalk between autophagy and apoptosis has attracted broader attention. Basal autophagy serves to maintain cell homeostasis, while the upregulation of this process is an element of stress response that enables the cell to survive under adverse conditions. Autophagy may also determine the fate of the cell through its interactions with cell death pathways. The protein networks that control the initiation and the execution phase of these two processes are highly interconnected. Several scenarios for the crosstalk between autophagy and apoptosis exist. In most cases, the activation of autophagy represents an attempt of the cell to cope with stress, and protects the cell from apoptosis or delays its initiation. Generally, the simultaneous activation of pro-survival and pro-death pathways is prevented by the mutual inhibitory crosstalk between autophagy and apoptosis. But in some circumstances, autophagy or the proteins of the core autophagic machinery may promote cellular demise through excessive self-digestion (so-called "autophagic cell death") or by stimulating the activation of other cell death pathways. It is controversial whether cells actually die via autophagy, which is why the term "autophagic cell death" has been under intense debate lately. This review summarizes the recent findings on the multilevel crosstalk between autophagy and apoptosis in aspects of common regulators, mutual inhibition of these processes, the stimulation of apoptosis by autophagy or autophagic proteins and finally the role of autophagy as a death-execution mechanism.

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

“…30 It was reported that PI3K/Akt/mTOR signaling pathway is involved in autophagy. 30 It was reported that PI3K/Akt/mTOR signaling pathway is involved in autophagy.…”

Fucoxanthin treatment inhibits nasopharyngeal carcinoma cell proliferation through induction of autophagy mechanism

“…Autophagy, programmed cell death type II occurs due to cellular stress, is characterized with numerous cytoplasmic autophagic vacuoles leading to non‐apoptotic cell death 24 . Although apoptosis and autophagy are considered to be a two distinctive cell death mechanism, cross talk between these pathways during cancer condition have been reported 25,26 . Therefore, developing a drug which induces autophagy in apoptosis resistant cancer cells will be more persuasive to treat recurring cancer.…”

Salvianolate lyophilized injection induced autophagy against neuronal apoptosis through the Akt/mTOR pathway in Neuro-2a cells

“…Autophagy is a dynamic process that decomposes the damaged organelles, abnormal proteins, and metabolic waste and then maintains the normal physiological microenvironment [37]. It is worth noting that autophagy is considered to be the self-protection mechanism of cells, but in some cases, autophagy may promote cellular demise through excessive self-digestion or stimulation of activation of other cell death pathways [38]. Recently, increasing evidence has supported that regulating autophagy is a mechanism of cerebral I/R injury [39][40][41].…”