---
title: "Mitochondrial dysfunction in neurology: biomarkers for diagnosis, stratification and monitoring"
id: "nature-reviews-neurology-0-mitochondrial-dysfunction-in-neurology-biomarkers-and-clinical-implications"
canonical_url: "https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-mitochondrial-dysfunction-in-neurology-biomarkers-and-clinical-implications"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "Nature Reviews Neurology"
source_url: "https://www.nature.com/articles/s41582-026-01274-z"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mitochondrial dysfunction in neurology: biomarkers for diagnosis, stratification and monitoring
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-mitochondrial-dysfunction-in-neurology-biomarkers-and-clinical-implications
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** Nature Reviews Neurology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41582-026-01274-z)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Mitochondrial dysfunction is recognized as a downstream pathogenic mechanism across a broad range of neurological disorders, from **primary mitochondrial diseases** to Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, multiple sclerosis, hereditary ataxias and idiopathic inflammatory myopathies. - The review frames **primary mitochondrial diseases** as proof-of-concept models that expose impaired oxidative phosphorylation and therefore help identify biomarkers with translational potential. - Investigators categorize mitochondrial biomarkers into four domains: **fluid biomarkers** reflecting metabolic shifts and stress signalling; **genetic biomarkers** measuring mtDNA integrity and dynamics; **multi-omics approaches** combining transcriptomic, proteomic and metabolomic data; and **imaging biomarkers** that assess structural and functional consequences in vivo. - Across disorders, data indicated recurring disturbances in bioenergetics, redox homeostasis, mitochondrial genome maintenance and inflammatory signalling. - The study team observed major barriers to clinical implementation: methodological heterogeneity across assays, substantial biological variability and reduced disease specificity of many candidate markers. - Authors noted that integrated, multimodal biomarker strategies and longitudinal validation are needed to support precision medicine, improve patient stratification and guide therapeutic development targeting mitochondrial pathways. - Standardized, multimodal biomarker panels are proposed as a route to improve diagnosis, monitoring and outcome assessment in both clinical practice and therapeutic neurology trials.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [nature reviews neurology](https://www.nature.com/nrneurol) 3. [review articles](https://www.nature.com/nrneurol/articles?type=review-article) 4. article * Review Article * Published: 23 October 2026 # Mitochondrial dysfunction in neurology: biomarkers and clinical implications * [Elena Rossini](https://www.nature.com/articles/s41582-026-01274-z#auth-Elena-Rossini-Aff1-Aff2) [ORCID: orcid.org/0009-0002-7862-6743](https://orcid.org/0009-0002-7862-6743)[1](https://www.nature.com/articles/s41582-026-01274-z#Aff1),[2](https://www.nature.com/articles/s41582-026-01274-z#Aff2), * [Matteo Garibaldi](https://www.nature.com/articles/s41582-026-01274-z#auth-Matteo-Garibaldi-Aff2)[2](https://www.nature.com/articles/s41582-026-01274-z#Aff2), * [Michael G. Hanna](https://www.nature.com/articles/s41582-026-01274-z#auth-Michael_G_-Hanna-Aff1-Aff3)[1](https://www.nature.com/articles/s41582-026-01274-z#Aff1),[3](https://www.nature.com/articles/s41582-026-01274-z#Aff3), * [Robert D. S. Pitceathly](https://www.nature.com/articles/s41582-026-01274-z#auth-Robert_D__S_-Pitceathly-Aff1-Aff3) [ORCID: orcid.org/0000-0002-6123-4551](https://orcid.org/0000-0002-6123-4551)[1](https://www.nature.com/articles/s41582-026-01274-z#Aff1),[3](https://www.nature.com/articles/s41582-026-01274-z#Aff3) [na1](https://www.nature.com/articles/s41582-026-01274-z#na1) & * … * [Chiara Pizzamiglio](https://www.nature.com/articles/s41582-026-01274-z#auth-Chiara-Pizzamiglio-Aff1-Aff3)[1](https://www.nature.com/articles/s41582-026-01274-z#Aff1),[3](https://www.nature.com/articles/s41582-026-01274-z#Aff3) [na1](https://www.nature.com/articles/s41582-026-01274-z#na1) Show authors [_Nature Reviews Neurology_](https://www.nature.com/nrneurol) (2026) [Cite this article](https://www.nature.com/articles/s41582-026-01274-z#citeas) Save article [ View saved research ](https://www.nature.com/saved-research) ## Abstract Mitochondrial dysfunction is increasingly recognized as a shared downstream pathogenic mechanism across a wide spectrum of neurological disorders, ranging from primary mitochondrial diseases to conditions including amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, multiple sclerosis, hereditary ataxias and idiopathic inflammatory myopathies. This Review examines the role of mitochondrial biomarkers in improving diagnostic accuracy, patient stratification and monitoring of disease progression and therapeutic response. Primary mitochondrial diseases are presented as proof-of-concept models of impaired oxidative phosphorylation, providing a framework for biomarker identification and validation with translational relevance to other neurological diseases. Mitochondrial biomarkers can be broadly categorized into four domains: fluid biomarkers, reflecting metabolic alterations and stress signalling; genetic biomarkers, capturing mitochondrial DNA integrity and dynamics; multi-omics approaches, integrating transcriptomic, proteomic and metabolomic signatures; and imaging biomarkers, enabling in vivo assessment of structural and functional consequences of mitochondrial dysfunction. Across disorders, these biomarkers reveal shared disturbances in bioenergetics, redox homeostasis, mitochondrial genome maintenance and inflammatory signalling. However, clinical implementation remains limited by methodological heterogeneity, biological variability and reduced disease specificity. Integrated, multimodal biomarker strategies, combined with longitudinal validation, will be essential for supporting precision medicine and guiding the development of therapies to target mitochondrial pathways in neurology. ## Key points * Mitochondrial dysfunction is a shared pathogenic mechanism across primary mitochondrial diseases and neurological disorders, including amyotrophic lateral sclerosis, Alzheimer disease, hereditary ataxias, idiopathic inflammatory myopathies, multiple sclerosis and Parkinson disease. * Primary mitochondrial diseases provide a proof-of-concept framework for identifying and validating mitochondrial biomarkers. * Fluid, genetic, multi-omics and imaging biomarkers capture complementary aspects of mitochondrial dysfunction. * Limited specificity, assay variability and lack of longitudinal validation remain major barriers to clinical implementation. * Standardized, multimodal biomarker panels may improve diagnosis, patient stratification and outcome assessment in both clinical practice and therapeutic neurological trials. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01274-z) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01274-z) Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27.99 € / 30 days cancel any time [Learn more](https://shop.nature.com/products/plus/?region=ROW) Subscribe to this journal Receive 12 print issues and online access 176.64 € per year only 14.72 € per issue [Learn more](https://www.nature.com/nrneurol/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/auth/personal/springernature?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01274-z) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: Overview of mitochondrial biomarkers.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41582-026-01274-z/MediaObjects/41582_2026_1274_Fig1_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Biomarkers](https://www.nature.com/subjects/biomarkers) * [Neuromuscular disease](https://www.nature.com/subjects/neuromuscular-disease) ## References 1. 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