Cell death: Machinery and regulation

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Regulated cell death is divided into apoptotic and nonapoptotic forms that exhibit different molecular mechanisms and signaling regulation. This chapter introduces different forms of regulated cell death with a more detailed discussion on apoptosis. Functionally, apoptosis is not only an essential part of development but also a mediator of tissue injury and dysfunction. Mechanically, apoptosis can be initiated by either the extrinsic cell death receptor or intrinsic mitochondrial pathways. Unlike necrosis, apoptosis is characterized by a number of morphological features, such as cell shrinkage, membrane blebbing, nuclear condensation, and DNA fragmentation. A biochemical hallmark of apoptosis is the activation of caspases, including initiator caspases (CASP2, CASP8, CASP9, and CASP10) and executioner caspases (CASP3, CASP6, and CASP7), which leads to cell death mainly through protein cleavages. The BCL2 family of proteins, including the pro-apoptotic (e.g., BAX, BAK1, BAD, and BID) and antiapoptotic (e.g., BCL2 and BCL2L1) BCL2 members, control mitochondrial outer membrane permeabilization and the subsequent release of mitochondrial proteins (e.g., CYCS, DIABLO, and HTRA2) leading to the activation of executioner caspases. Moreover, the cleavage of BID by CASP8 is a molecular event linking the extrinsic apoptosis pathway to the intrinsic apoptosis pathway. Additionally, inhibitor-of-apoptosis proteins and heat shock proteins function as negative regulators of apoptosis through the inhibition of caspase activity, mainly via the protein-protein interaction. Understanding the process and function of apoptosis could open new opportunities for disease therapy.

Original languageEnglish (US)
Title of host publicationMechanisms of Cell Death and Opportunities for Therapeutic Development
PublisherElsevier
Pages47-64
Number of pages18
ISBN (Electronic)9780128142080
ISBN (Print)9780128142097
DOIs
StatePublished - Jan 1 2022

Keywords

  • Apoptosis
  • BCL2
  • Caspase
  • Heat shock protein
  • Inhibitor of apoptosis protein
  • Regulated cell death

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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