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Mechanical insights into the regulation of programmed cell death by p53 via mitochondria

Kohji Yamada1, Kiyotsugu Yoshida1

  • 1Department of Biochemistry, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.

Biochimica Et Biophysica Acta. Molecular Cell Research
|February 22, 2019
PubMed

Insights

Programmed cell deaths (PCDs) are crucial for life and disease, often involving the tumor suppressor p53 and mitochondria. This review details p53

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Programmed cell deaths (PCDs) are essential biological processes for development and homeostasis, but their dysregulation contributes to diseases.
  • Mitochondria play a central role in various PCD pathways, acting as key regulators of cell fate.
  • The tumor suppressor protein p53 is increasingly recognized as a critical mediator in diverse PCDs, influencing their initiation and execution.

Purpose of the Study:

  • To provide a comprehensive review of programmed cell death mechanisms involving the mitochondria.
  • To elucidate the multifaceted roles of the tumor suppressor p53 in various PCD pathways.
  • To discuss how p53's intracellular localization influences the induction of different PCDs under cellular stress.

Main Methods:

  • Literature review of recent research on p53 and mitochondrial involvement in programmed cell death.
  • Analysis of studies focusing on the intracellular localization of p53 in response to cellular stress.
  • Synthesis of information on classical apoptosis, non-classical apoptosis, autophagic cell death, ferroptosis, and necroptosis.

Main Results:

  • Most programmed cell deaths involve p53 and mitochondrial components.
  • The intracellular positioning of p53 is a key determinant for the induction of specific PCD pathways.
  • p53's function in PCD is diverse, ranging from classical apoptosis to ferroptosis and necroptosis.

Conclusions:

  • p53 is a pivotal regulator of mitochondrial-mediated programmed cell death pathways.
  • Understanding p53's localization-dependent roles in PCD is crucial for comprehending development, homeostasis, and disease.
  • This review consolidates current knowledge on p53-driven PCD, highlighting its significance in cellular fate determination.
Keywords:
ApoptosisMitochondriaNecroptosisProgrammed cell deathp53

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