Autophagy/Mitophagy Regulated by Ubiquitination: A Promising Pathway in Cancer Therapeutics

Seung-Cheol Jee1, Heesun Cheong1

  • 1Division of Cancer Biology, Research Institute, National Cancer Center, Goyang-si 10408, Republic of Korea.

Cancers
|February 25, 2023
PubMed

Insights

Autophagy and mitophagy are crucial cellular processes with dual roles in cancer. Their regulation by ubiquitination offers potential therapeutic targets for cancer treatment.

Area of Science:

  • Cellular Biology
  • Oncology
  • Biochemistry

Background:

  • Autophagy and mitophagy are vital for cellular homeostasis, organelle quality control, and energy balance.
  • These processes play complex, context-dependent roles in both promoting and inhibiting tumor progression.
  • Dysregulation of autophagy and mitophagy is implicated in various stages of cancer development.

Purpose of the Study:

  • To review the mechanistic links between cancer development and autophagy/mitophagy.
  • To explore the role of ubiquitination and deubiquitination in regulating these pathways in cancer.
  • To identify potential therapeutic targets within the autophagy and mitophagy machinery.

Main Methods:

  • Literature review focusing on mechanistic associations.
  • Analysis of the role of ubiquitin modification in autophagy and mitophagy.
  • Discussion of proteins involved in cancer-related autophagy/mitophagy.

Main Results:

  • Mitophagy exhibits dual roles in tumors: supporting growth by clearing damaged mitochondria or inhibiting growth by reducing reactive oxygen species (ROS).
  • Ubiquitination and deubiquitination are key regulatory modifications impacting autophagy and mitophagy machinery.
  • Numerous E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) modulate these pathways, influencing cancer progression.

Conclusions:

  • The intricate relationship between autophagy, mitophagy, and cancer is heavily influenced by ubiquitination.
  • Understanding these ubiquitin-modified pathways is critical for developing novel cancer therapies.
  • Specific proteins involved in cancer-associated autophagy and mitophagy represent promising therapeutic targets.

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