Mitochondrial ROS Production at Complexes I and III in Human Myocardium and Skeletal Muscle: A Distinct Pattern Compared with Rat Tissue.
Level 5 - mechanism / opinion, no new human data
Ex vivo bench and animal comparative tissue research
PubMed 42121930 · doi:10.3390/cells15090830
What was done
Researchers directly measured mitochondrial reactive oxygen species (ROS; hydrogen peroxide via Amplex UltraRed) and oxygen consumption (Clark-type electrode) in human myocardial and skeletal muscle biopsies compared with rat tissues under identical experimental conditions. They evaluated ROS generation across three pathways: forward electron transport at complex I, reverse electron transport at complex I, and the ubiquinol oxidation site of complex III.
What was found
Rat tissues produced more absolute ROS than human tissues across all mechanisms, consistent with higher respiratory rates. However, the dominant site of ROS production differed between species: complex III was the primary source in rats, whereas reverse electron transport at complex I was the dominant source in human myocardium and skeletal muscle. When normalized to respiration, human tissues showed relatively greater ROS generation at complex I but markedly lower production at complex III compared with rat tissues. The abstract reports directional findings without numerical values, effect sizes, or confidence intervals.
Why it matters
These findings identify fundamental species differences in mitochondrial ROS generation mechanisms, providing a plausible explanation for why cardioprotective interventions targeting ROS in rodent models frequently fail in human trials.
Limits
The abstract does not disclose sample sizes, patient clinical characteristics, or underlying cardiac pathologies of the human donors. As an ex vivo biopsy study under controlled substrate conditions, findings may not fully capture in vivo physiology or acute ischemia/reperfusion dynamics.
Cited by
- supports Mitochondria are the primary generator of reactive oxygen species in cells.