Thermotolerance induced by non-lethal heat shock at 40 °C is activated by mitochondrial ROS and is Nrf2-dependent.
Level 5 - mechanism / opinion, no new human data
Bench research in vitro cell culture model
PubMed 41489545 · doi:10.1016/j.abb.2025.110649
What was done
HeLa cells were exposed in vitro to mild heat stress (40 °C) or lethal heat shock (≥42 °C) to evaluate mechanisms of adaptive thermotolerance. Investigators measured cellular and mitochondrial superoxide and peroxide levels. They pharmacologically inhibited ROS sources using the mitochondrial antioxidant MitoQ and NADPH oxidase inhibitor apocynin, and modulated Nrf2 expression through overexpression and knockdown to evaluate cell survival and apoptotic death under heat stress.
What was found
Exposure to 42 °C increased cellular and mitochondrial superoxide and peroxide in HeLa cells, whereas MitoQ and apocynin reduced ROS levels and apoptotic cell death. Mild heat exposure at 40 °C increased ROS production and reduced cell death following subsequent 42 °C challenge. Nrf2 expression correlated directly with the protective thermotolerant response induced by 40 °C pre-treatment. Pre-treatment with MitoQ before 40 °C heating reduced Nrf2 levels and eliminated the thermotolerant protection against 42 °C toxicity. The abstract reported directional mechanistic findings without providing quantitative numbers.
Why it matters
This study identifies mitochondrial ROS and Nrf2 signaling as key mediators of cellular thermotolerance induced by mild hyperthermia. Targeting this pathway could help prevent adaptive resistance to clinical hyperthermia during cancer therapy.
Limits
This is purely an in vitro study conducted in a single immortalized cancer cell line (HeLa), with no in vivo animal models or human clinical data. The abstract reports no numerical values, effect sizes, exposure times, or statistical metrics.
Cited by
- supports Heat exposure, such as from saunas or exercise, increases the Nrf2 pathway.