The Review examines how mitochondrial biomarkers could improve diagnostic accuracy, patient stratification and the monitoring of disease progression and therapeutic response. Rather than presenting new experimental data, the authors synthesize existing evidence and present primary mitochondrial diseases as proof-of-concept models of impaired oxidative phosphorylation, offering a framework for biomarker identification and validation with translational relevance to other neurological diseases.

The authors organize mitochondrial biomarkers into four broad domains. Fluid biomarkers reflect metabolic alterations and stress signalling; genetic biomarkers capture mitochondrial DNA integrity and dynamics; multi-omics approaches integrate transcriptomic, proteomic and metabolomic signatures; and imaging biomarkers enable in vivo assessment of the structural and functional consequences of mitochondrial dysfunction. Across disorders, these biomarkers reveal shared disturbances in bioenergetics, redox homeostasis, mitochondrial genome maintenance and inflammatory signalling.

Despite this unifying picture, the Review is explicit that clinical implementation remains limited. The authors identify methodological heterogeneity, biological variability and reduced disease specificity as major barriers, alongside a lack of longitudinal validation. In other words, while mitochondrial measures consistently point to common biological disturbances, they do not yet reliably distinguish one neurological disease from another or track individual patients over time in a standardized way.

To address these gaps, the authors argue that integrated, multimodal biomarker strategies, combined with longitudinal validation, will be essential for supporting precision medicine and guiding the development of therapies that target mitochondrial pathways in neurology. Standardized, multimodal biomarker panels may, they suggest, improve diagnosis, patient stratification and outcome assessment in both clinical practice and therapeutic neurological trials. The Review thus frames mitochondrial biomarkers less as a ready-made clinical tool and more as a developing framework whose value depends on rigorous, standardized and long-term validation across disease types.

Subject of Research: Mitochondrial biomarkers and their clinical implications across neurological disorders

Article Title: Mitochondrial dysfunction in neurology: biomarkers and clinical implications

Article References: Rossini, E., Garibaldi, M., Hanna, M. G., Pitceathly, R. D. S., & Pizzamiglio, C. (2026). Mitochondrial dysfunction in neurology: biomarkers and clinical implications. Nature Reviews Neurology. https://doi.org/10.1038/s41582-026-01274-z

Image Credits: AI Generated

DOI: 10.1038/s41582-026-01274-z

Keywords: mitochondrial dysfunction, neurology, biomarkers, primary mitochondrial diseases, Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, multiple sclerosis, hereditary ataxias, oxidative phosphorylation, precision medicine, Nature Reviews Neurology