Autophagic cell death and cancer

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Abstract

Programmed cell death (PCD) is a crucial process required for the normal development and physiology of metazoans. The three major mechanisms that induce PCD are called type I (apoptosis), type II (autophagic cell death), and type III (necrotic cell death). Dysfunctional PCD leads to diseases such as cancer and neurodegeneration. Although apoptosis is the most common form of PCD, recent studies have provided evidence that there are other forms of cell death. One of such cell death is autophagic cell death, which occurs via the activation of autophagy. The present review summarizes recent knowledge about autophagic cell death and discusses the relationship with tumorigenesis. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Figures

  • Figure 1. Molecular mechanism of apoptosis and autophagic cell death. An increase in the permeability of the outer mitochondrial membrane is crucial for apoptosis to occur and is regulated by multidomain pro-apoptotic members of the Bcl-2 family (Bax and Bak), resulting in the release of cytochrome c into the cytoplasm. Then, cytochrome c associates with apoptotic protease activating factor-1 (Apaf-1), which activates the caspase cascade to execute apoptotic cell death. Apoptosis-associated mitochondrial membrane permeability is primarily controlled by Bcl-2 family members. When apoptosis is blocked, various apoptotic stimuli activate autophagy and c-Jun N-terminal kinase (JNK), resulting in the induction of autophagic cell death.
  • Figure 2. Hypothetical model of macroautophagy. There are at least two modes of macroautophagy, i.e., conventional and alternative macroautophagy. Conventional macroautophagy depends on Atg5 and Atg7, is associated with light chain 3 (LC3) modification and may originate from Endoplasmic reticulum (ER)-mitochondria contact membrane. In contrast, alternative macroautophagy occurs independent of Atg5 or Atg7 expression and LC3 modification. The generation of autophagic vacuoles in this type of macroautophagy may originate from Golgi membrane and late endosomes (LE) in a Rab9-dependent manner. Although both these processes lead to bulk degradation of damaged proteins or organelles by generating autolysosomes, they seem to be activated by different stimuli, in different cell types and have different physiological roles.

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CITATION STYLE

APA

Shimizu, S., Yoshida, T., Tsujioka, M., & Arakawa, S. (2014, February 21). Autophagic cell death and cancer. International Journal of Molecular Sciences. Molecular Diversity Preservation International. https://doi.org/10.3390/ijms15023145

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