APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells

Area of Science:

• Cell Biology
• Ophthalmology
• Molecular Biology

Background:

• Retinal pigment epithelial (RPE) cell dysfunction is central to age-related macular degeneration (AMD).
• The function of Apoptosis-related protein 3 (APR3), identified after all-trans retinoic acid treatment, is largely unknown in RPE cells.

Purpose of the Study:

• To elucidate the role of APR3 in regulating oxidative stress and mitochondrial function in RPE cells.
• To investigate APR3's potential as a therapeutic target for age-related macular degeneration.

Main Methods:

• Investigated APR3 interaction with nuclear factor (erythroid-derived 2)-like 2 (NFE2L2).
• Utilized APR3 knockdown and overexpression in ARPE-19 cells.
• Assessed redox status, mitochondrial activity, oxygen consumption, ATP content, and reactive oxygen species (ROS) production.

Main Results:

• APR3 knockdown enhanced NFE2L2 nuclear translocation, upregulated phase II enzymes, and improved redox/mitochondrial status.
• APR3 overexpression localized to mitochondria, increased ROS, impaired mitochondrial respiration, and reduced ATP, leading to apoptosis.
• High-dose all-trans retinoic acid increased APR3 and ROS, decreasing ATP; these effects were abrogated by APR3 knockdown.

Conclusions:

• APR3 critically regulates cellular redox balance and mitochondrial function.
• APR3's role in oxidative stress and mitochondrial dysfunction suggests it as a potential therapeutic target for AMD.