Related Experiment Video
Updated: Jun 18, 2026
Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
Published on: May 5, 2022
[Peripheral neuropathies due to mitochondrial disorders]
1Centre de référence des neuropathies périphériques rares, CHU de Limoges, 2, avenue Martin-Luther-King, 87042 Limoges cedex, France. benoit.funalot@unilim.fr
Abstract:
Involvement of peripheral nerves is frequent in mitochondrial disorders but with variable severity. Mitochondrial diseases causing peripheral neuropathies (PN) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. Genetically-determined PN due to mutations of mitofusin 2, a GTPase involved in the fusion of external mitochondrial membranes, were identified during the last few years. Characteristic ultrastructural lesions (abnormalities of axonal mitochondria) are observed on longitudinal sections of nerve biopsies in patients with PN due to mitofusin 2 mutations.
Insights
Peripheral neuropathies (PN) are common in mitochondrial disorders. Genetic mutations affecting mitochondrial DNA or nuclear genes, like POLG and TYMP, cause varied PN severity and characteristic nerve biopsy lesions.
Area of Science:
- Neurology
- Genetics
- Mitochondrial Biology
Context:
- Peripheral neuropathies (PN) frequently occur in mitochondrial disorders.
- PN severity varies greatly, stemming from mitochondrial DNA (mtDNA) or nuclear gene mutations.
Purpose:
- To explore the genetic basis and pathological mechanisms of mitochondrial disorders causing peripheral neuropathy.
- To highlight specific genetic defects, including mutations in POLG, TYMP, and mitofusin 2, and their impact on mtDNA maintenance and mitochondrial structure.
Summary:
- Mitochondrial diseases can lead to PN through direct mtDNA mutations (e.g., MERRF, MELAS) or nuclear gene defects impacting mtDNA maintenance (e.g., SANDO, MNGIE).
- Mutations in nuclear genes like POLG and TYMP result in secondary mtDNA abnormalities, contributing to PN.
- Defects in mitofusin 2, crucial for mitochondrial membrane fusion, also cause genetically determined PN with distinctive axonal mitochondrial ultrastructural changes.
Impact:
- Advances understanding of the diverse genetic etiologies of peripheral neuropathies in mitochondrial diseases.
- Identifies key genes and molecular pathways involved in mitochondrial dysfunction and neurological damage.
- Provides insights into potential diagnostic markers and therapeutic targets for mitochondrial disorders affecting the peripheral nervous system.
Related Concept Videos
01:22Diabetic Neuropathy
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
01:28Disorders of the Nervous Tissue
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...
01:21Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation
01:48ATP Synthase: Mechanism
01:37Mitochondria