Mitochondrial disease: mechanisms, signalling, and therapeutic opportunities.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search methodology or original human data.
PubMed 42250784 · doi:10.1016/j.freeradbiomed.2026.06.013
What was done
This is a narrative review synthesizing current concepts in mitochondrial disease pathophysiology. The authors discuss oxidative phosphorylation impairment, bioenergetic deficits, clinical heterogeneity, the dual role of reactive oxygen species (ROS) in cellular damage versus signalling, and experimental tools such as alternative oxidase (AOX) used in preclinical research.
What was found
The abstract reports no numerical findings or quantitative effect sizes. It describes qualitative mechanistic pathways showing that nuclear or mitochondrial DNA mutations disrupt ATP synthesis and redox homeostasis, and notes that ROS exert context-dependent signalling effects that vary by cell type, subcellular localization, and concentration.
Why it matters
It outlines critical mechanistic gaps in understanding mitochondrial disease heterogeneity and highlights how nuanced redox signalling complicates therapy development, pointing to preclinical tools for future translation.
Limits
As a non-systematic narrative review, it presents no original clinical or experimental data. The mechanistic and therapeutic strategies discussed rely primarily on preclinical models, and no empirical patient outcomes or sample sizes are evaluated.
Cited by
- supports Mitochondria contain their own DNA, and mutations in this genetic code can disrupt ATP synthesis, leading to mitochondrial diseases.