TERT's protective effect on trophoblast cells: Reducing mitochondrial ROS

Area of Science:

• Cell Biology
• Mitochondrial Biology
• Reproductive Biology

Background:

• Placental trophoblast dysfunction and mitochondrial dysfunction are linked to pregnancy complications.
• Telomerase reverse transcriptase (TERT) plays a role in cellular health and repair.

Purpose of the Study:

• To investigate the protective role of telomerase reverse transcriptase (TERT) against placental trophoblast and mitochondrial dysfunction.
• To determine if mitochondrial localization of TERT is crucial for its protective effects.

Main Methods:

• An oxidative stress model was induced in HTR-8/SVneo cells using hydrogen peroxide (H2O2).
• TERT expression was manipulated via lentiviral transfection (overexpression and empty vector).
• The Src kinase inhibitor PP1 was used to block TERT mitochondrial translocation.
• Cellular functions, oxidative stress markers, and mitochondrial integrity were assessed.

Main Results:

• TERT overexpression reduced reactive oxygen species (ROS), improved cell viability, migration, and invasion.
• Mitochondrial function, including membrane potential, ATP production, and ultrastructure, was preserved in TERT-overexpressing cells.
• Inhibition of mitochondrial TERT translocation with PP1 abolished these protective effects, worsening oxidative stress and cell damage.

Conclusions:

• Elevated mitochondrial TERT mitigates oxidative stress-induced cellular damage by stabilizing mitochondria.
• Targeting mitochondrial TERT offers a potential therapeutic strategy for pregnancy-related disorders.