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Updated: Sep 28, 2025

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

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PCNA negatively regulates MITA through the autophagy pathway in miiuy croaker (Miichthys miiuy)

Han Zhang1, Ya Chen1, Junxia Cui1

  • 1Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.

Fish & Shellfish Immunology
|April 3, 2022
PubMed

Insights

Proliferating Cell Nuclear Antigen (PCNA) regulates the innate immune response by degrading MITA via autophagy. This mechanism prevents excessive immune reactions, offering insights into immune pathway regulation in vertebrates.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • The innate immune response, crucial for defense against pathogens, is initiated by interferon signaling.
  • MITA protein activates interferon expression, promoting antiviral innate immunity.
  • Tight regulation of innate immunity is essential to prevent host self-damage from over-immunization.

Purpose of the Study:

  • To investigate the role of Proliferating Cell Nuclear Antigen (PCNA) in regulating MITA and interferon-mediated immune responses.
  • To elucidate the mechanism by which PCNA influences MITA stability and subsequent immune signaling.

Main Methods:

  • Overexpression of PCNA in cells to observe its effect on MITA levels.
  • Utilizing the autophagy inhibitor 3-MA to assess the involvement of the autophagy pathway in PCNA-mediated MITA degradation.
  • Monitoring interferon expression levels in response to PCNA manipulation.

Main Results:

  • PCNA overexpression leads to decreased MITA levels and reduced interferon expression.
  • The autophagy inhibitor 3-MA partially blocks PCNA-induced MITA degradation, confirming the involvement of autophagy.
  • PCNA targets MITA for degradation through the autophagy pathway, thereby inhibiting interferon production.

Conclusions:

  • PCNA negatively regulates MITA stability and interferon production via the autophagy pathway.
  • PCNA acts as a negative regulator in the innate immune response, preventing excessive immune reactions.
  • These findings provide novel insights into the regulatory mechanisms of immune signaling pathways, particularly in lower vertebrates.
Keywords:
AutophagyIFNMITANegative regulationPCNA

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