Mitochondrial complex I as a master regulator of redox signaling: From structural architecture to directionality of electron transport.
Level 5 - mechanism / opinion, no new human data
Narrative review of structural and mechanistic bench literature with no primary human data.
PubMed 42191039 · doi:10.1016/j.freeradbiomed.2026.05.311
What was done
This narrative review synthesizes literature on mitochondrial complex I (MCI) structural architecture and operational mechanics, incorporating recent cryo-EM structural determinations, time-resolved studies, and multiscale molecular dynamics simulations to examine directional electron transport and redox signaling.
What was found
The abstract reports no numerical data or statistical metrics. It describes qualitative mechanistic pathways: forward electron transport (FET) drives oxidative phosphorylation and ATP synthesis, whereas reverse electron transport (RET)—driven by elevated membrane potential and ubiquinol pool reduction—transfers electrons from ubiquinol to NAD+ and produces ROS. It notes that MCI-derived ROS and NAD+/NADH changes modulate hypoxia sensing, immune activation, and stem-cell metabolism under physiological conditions, while contributing to ischemia-reperfusion injury, cancer, neurodegeneration, and aging when dysregulated.
Why it matters
The paper provides a unifying conceptual model connecting near-atomic structural biology of complex I with its bidirectional redox signaling functions in health and disease.
Limits
The abstract describes a narrative review rather than a systematic review or primary empirical study. No quantitative data, sample sizes, or study selection criteria are reported.
Cited by
- supports Nicotinamide adenine dinucleotide (NAD+) acts as a primary electron carrier in cellular metabolism, transferring electrons derived from nutrients to the mitochondrial electron transport chain.