Related Experiment Video

Updated: Sep 21, 2025

Assessment of Oxidative Damage in the Primary Mouse Ocular Surface Cells/Stem Cells in Response to Ultraviolet-C UV-C Damage
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Assessment of Oxidative Damage in the Primary Mouse Ocular Surface Cells/Stem Cells in Response to Ultraviolet-C UV-C Damage

Published on: February 15, 2020

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REDD1 interacts with AIF and regulates mitochondrial reactive oxygen species generation in the keratinocyte response

Robert P Feehan1, Catherine S Coleman1, Shauna Ebanks1

  • 1Department of Cellular & Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.

Biochemical and Biophysical Research Communications
|May 31, 2022
PubMed

Insights

Regulated in DNA Damage and Development 1 (REDD1) protects skin cells from UVB damage by maintaining mitochondrial function. Loss of REDD1 increases cell death and reactive oxygen species, highlighting its role in preventing non-melanoma skin cancer.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Non-melanoma skin cancer (NMSC) incidence is increasing, particularly in immunocompromised individuals like organ transplant recipients.
  • Understanding pathways driving NMSC is crucial for developing new prevention and treatment strategies.
  • Regulated in DNA Damage and Development 1 (REDD1) is a stress-induced protein known to regulate mTORC1 and mitochondrial function.

Purpose of the Study:

  • To investigate the role of REDD1 in the cellular response to ultraviolet B (UVB) radiation.
  • To determine if REDD1 influences UVB-induced apoptosis and mitochondrial function in human keratinocytes.

Main Methods:

  • Utilized REDD1 knockout human keratinocytes.
  • Assessed sensitivity to UVB-induced apoptosis.
  • Measured mitochondrial reactive oxygen species (ROS) generation.
  • Quantified levels of apoptosis-inducing factor (AIF) and its interaction with REDD1 and CHCHD4.

Main Results:

  • REDD1 knockout keratinocytes showed increased sensitivity to UVB-induced apoptosis, independent of mTORC1.
  • Loss of REDD1 intensified mitochondrial ROS production.
  • REDD1 knockout led to reduced levels of apoptosis-inducing factor (AIF).
  • REDD1 was found to interact with AIF and CHCHD4, a protein crucial for oxidative phosphorylation (OXPHOS).

Conclusions:

  • REDD1 plays a protective role in human keratinocytes against UVB-induced oxidative stress.
  • REDD1 appears to be part of a mitochondrial complex that mitigates ROS toxicity.
  • These findings suggest REDD1 and its interacting partners are potential therapeutic targets for NMSC prevention and treatment.
Keywords:
AIFApoptosisNon-melanoma skin cancerREDD1UVBmTOR

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