Life and Death Decisions—The Many Faces of Autophagy in Cell Survival and Cell Death

Abstract

Autophagy is a process conserved from yeast to humans. Since the discovery of autophagy, its physiological role in cell survival and cell death has been intensively investigated. The inherent ability of the autophagy machinery to sequester, deliver, and degrade cytoplasmic components enables autophagy to participate in cell survival and cell death in multiple ways. The primary role of autophagy is to send cytoplasmic components to the vacuole or lysosomes for degradation. By fine-tuning autophagy, the cell regulates the removal and recycling of cytoplasmic components in response to various stress or signals. Recent research has shown the implications of the autophagy machinery in other pathways independent of lysosomal degradation, expanding the pro-survival role of autophagy. Autophagy also facilitates certain forms of regulated cell death. In addition, there is complex crosstalk between autophagy and regulated cell death pathways, with a number of genes shared between them, further suggesting a deeper connection between autophagy and cell death. Finally, the mitochondrion presents an example where the cell utilizes autophagy to strike a balance between cell survival and cell death. In this review, we consider the current knowledge on the physiological role of autophagy as well as its regulation and discuss the multiple functions of autophagy in cell survival and cell death.

Vacuolar Processing Enzymes in Plant Programmed Cell Death and Autophagy

“…Autophagic death is a controversial idea that has been discussed and debated many times. Autophagy is considered as a two-faced process: it can ensure cell survival as well as promote cell death [ 86 ]. However, it is difficult to distinguish when the occurrence of autophagic-related structures and recruitment of Atg genes function with the aim of cell survival and, conversely, when the aim is cell death.…”

“…Therefore, crosstalk between these two processes remains important to study. Many genes are involved in both autophagy and cell death in animal models [ 86 ]. Although our knowledge of this subject in plants is limited, a few examples of cell death with autophagy have been described, and VPEs, as proteases associated with cell death execution in plants, may be an important factor connected with the pro-death or pro-survival role of plant autophagy [ 25 , 32 ].…”

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

“…Selective autophagy processes contain proteins and specialized autophagic receptors which identify the cargo, generally mediated via cargo ubiquitination [ 30 ]. Through its interaction with a scaffold protein, the receptor either binds to cargoes or may be an integral component of these cargoes, connecting them to the autophagy machinery in the cell [ 31 ]. Protein aggregates are associated with Alzheimer’s, Parkinson’s, and Huntington’s diseases [ 2 , 32 ].…”

The Yin and Yang dualistic features of autophagy in thermal burn wound healing

“… 112 , 114 Autophagic cell death describes an “excessive” degradation of important cellular components that are necessary for the normal cell function. 115 – 117 This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy.…”

“… 122 – 125 Recent studies outlined the hypothesis that ROS are pawns with decisive roles in the fate of the molecular match of autophagic cell death. 114 – 116 It has been shown that the released lysosomal cathepsins have been involved in the oxidative stress–induced apoptosis. 122 – 125 Moreover, since lysosomes represent important sources of ROS, they might play important performances in the redox imbalance initiation and the exacerbation of oxidative stress, triggering oxidative cellular damages.…”