Interconnected neural networks with glowing mitochondria, representing energy and dysfunction in the brain.

Unraveling the Mystery: Multiple Sclerosis Linked to Mitochondrial Dysfunction

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Rhea Morgan in Health & Wellness October 2026 • 4 min read.

"Exploring the Connection Between Mitochondrial Disorders and Relapsing-Remitting Multiple Sclerosis"


Mitochondrial disease can manifest clinically as a diverse range of neurological syndromes, from devastating paediatric encephalomyopathies to slowly progressive paralysis of the external eye muscles in later life. This broad spectrum of presentations poses diagnostic challenges and highlights the complex role of mitochondria in overall health.

Could impairment in mitochondrial function be a risk factor for developing and progressing multiple sclerosis (MS)? This is a sensible question, especially when considering that mitochondria are not only the eukaryotic cell's chemical battery but also components involved in oxidative stress and programmed cell death pathways.

A new study sheds light on this connection, reporting the coexistence of relapsing multiple sclerosis with progressive external ophthalmoplegia. This clinical syndrome can result from various mitochondrial or nuclear genetic defects, leading to mitochondrial dysfunction. Understanding this link may offer new avenues for therapeutic intervention.

Decoding the Mitochondrial-MS Connection: What Does the Research Say?

Interconnected neural networks with glowing mitochondria, representing energy and dysfunction in the brain.

The association between mitochondrial dysfunction and MS might be coincidental, but prior research has implicated mitochondrial dysfunction as a pathological factor in central nervous system demyelination. There is some epidemiological evidence that Leber's hereditary optic neuropathy (LHON) and relapsing multiple sclerosis coincide 50 times more often than expected by chance.

Multiple sclerosis-like white matter lesions can be found on brain magnetic resonance imaging (MRI) scans of patients with confirmed LHON, particularly in females. This suggests a shared pathological mechanism between the two conditions. Mechanistically, mitochondrial dysfunction may predispose individuals to axonal loss in progressive multiple sclerosis.

  • Oxidative Stress: Mitochondria play a key role in managing oxidative stress, which can damage cells and contribute to MS.
  • Energy Production: Impaired mitochondrial function reduces cellular energy production, affecting nerve cells' ability to function properly.
  • Cell Death Pathways: Dysfunctional mitochondria can trigger programmed cell death, contributing to the loss of nerve cells in MS.
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Emerging Research

Recent research describes multiple sclerosis as a heterogeneous neuroinflammatory disease with diverse clinical presentations and accompanying neurodegenerative pathology. A 2025 review identifies a bidirectional interplay between mitochondrial dysfunction and lipid dysregulation as a factor in MS progression. Another 2025 review highlights epigenetic modifications and mitochondrial dysfunction in MS onset and progression, while noting that the exact causes remain unclear.

Evidence and Limitations

Evidence linking mitochondrial dysfunction to MS-related neurodegeneration includes post-mortem findings in lesioned areas, normal-appearing white matter, and nonlesional cortex. However, the etiology of MS remains elusive, involving a complex interplay of genetic and environmental factors. Reviews therefore present mitochondrial dysfunction as an important factor in MS pathogenesis and progression, but ongoing study is still needed to clarify the disease's underlying mechanisms.

Relapse Patterns and Treatment Risk

Relapsing-remitting MS is reported as the most common MS type, affecting approximately 85% of patients. A separate report describes three patients with a very active form of relapsing-remitting MS who experienced severe worsening a few days after their first natalizumab infusion. The cases were associated with a marked increase in brain inflammation, illustrating that relapse patterns and treatment-related outcomes can vary substantially among patients.

Protecting or augmenting mitochondrial function may therefore be a viable target for neuroprotective drugs. The publication of these two cases should bolster interest in this area of research and may lead to heightened recognition and reporting of this comorbidity. This could lead to more effective treatments and better patient outcomes.

Looking Ahead: The Future of MS Research and Mitochondrial Function

The insights from this research highlight the intricate relationship between mitochondrial health and neurological conditions like MS. By understanding the role of mitochondria in disease progression, researchers can develop targeted therapies to improve patient outcomes. As research continues, there is hope for innovative treatments that address the root causes of MS and other related disorders, offering renewed hope for those affected.

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Mitochondria, Oxidative Stress, and Immunity

Research on MS has increasingly emphasized mitochondrial processes in disease pathogenesis. One review identifies oxidative stress as a consequence of mitochondrial dysfunction and examines its impact in MS. Studies also report abnormalities in mitochondrial activity, metabolism, mitochondrial DNA levels, and mitochondrial morphology in immune cells from people with MS, supporting a connection between mitochondrial dysfunction and immune-system abnormalities.

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1177/1352458518816621, Alternate LINK

Title: Clinical Commentary On ‘Relapsing Remitting Multiple Sclerosis In Progressive External Ophthalmoplegia: A Report Of Two Cases’

Subject: Neurology (clinical)

Journal: Multiple Sclerosis Journal

Publisher: SAGE Publications

Authors: Lucy Matthews

Published: 2018-12-17

Everything You Need To Know

1

What is mitochondrial dysfunction, and how does it relate to multiple sclerosis?

Mitochondrial dysfunction is a condition where the mitochondria, the powerhouses of the cell, are not functioning correctly. This can lead to a variety of neurological syndromes. In the context of multiple sclerosis (MS), it's being investigated as a potential factor in the development and progression of the disease. The implications are significant because mitochondrial dysfunction can disrupt energy production, increase oxidative stress, and trigger cell death, all of which can contribute to the damage seen in MS.

2

Why is the link between mitochondrial dysfunction and multiple sclerosis considered important?

The connection between mitochondrial dysfunction and MS is significant due to the potential shared pathological mechanisms. Studies have shown that Leber's hereditary optic neuropathy (LHON) and relapsing multiple sclerosis co-occur more frequently than expected. Also, mitochondrial dysfunction can cause oxidative stress, leading to axonal loss. Understanding this link is important for developing targeted therapies. Targeting mitochondrial function may become a viable option for neuroprotective drugs.

3

What is the role of oxidative stress in the context of mitochondrial dysfunction and multiple sclerosis?

Oxidative stress plays a critical role in the context of mitochondrial dysfunction and MS. Mitochondria are involved in managing oxidative stress. In MS, oxidative stress can damage cells. This cellular damage can contribute to the loss of nerve cells and the progression of the disease. The implications are that by managing and reducing oxidative stress, it might be possible to slow down or halt the progression of MS. Research is focusing on this aspect to develop better treatments.

4

Does mitochondrial dysfunction lead to axonal loss in multiple sclerosis?

Yes, the research suggests a link between mitochondrial dysfunction and axonal loss in MS, specifically in progressive multiple sclerosis. Dysfunction within the mitochondria can trigger programmed cell death which contributes to the loss of nerve cells. The implications of this are that treatments designed to protect or augment mitochondrial function could potentially be neuroprotective, preserving nerve cells and mitigating the effects of MS. This opens new avenues for therapeutic intervention.

5

What are the potential implications of this research for the future of MS treatment?

The research suggests that addressing mitochondrial function could lead to improved treatments and outcomes. The insights highlight the intricate relationship between mitochondrial health and neurological conditions like MS. The implications involve the potential for innovative treatments that address the root causes of MS. This could lead to improved treatments, recognizing the comorbidity, and offering renewed hope for those affected. The future of MS research may involve developing targeted therapies aimed at improving mitochondrial function.

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