Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec:45:105235.
doi: 10.1016/j.nmd.2024.105235. Epub 2024 Oct 25.

Mitochondrial disorders are associated with morphological neuromuscular junction defects

Lola E R Lessard  1 , Emmanuelle Girard  2 , Nathalie Streichenberger  3 , Philippe Petiot  4 , Cécile Acquaviva  5 , Cécile Pagan  5 , Peter Mulligan  6 , Françoise Bouhour  1 , Laurent Schaeffer  7 , Arnaud Jacquier  8
Affiliations

Mitochondrial disorders are associated with morphological neuromuscular junction defects

Lola E R Lessard et al. Neuromuscul Disord. 2024 Dec.

Abstract

We aimed to evaluate whether inherited mitochondrial dysfunction is associated with neuromuscular junction remodeling in patients with mitochondrial disorders. Muscle biopsies from 15 patients with mitochondrial disorders and 10 control patients were analyzed through immunostaining for various neuromuscular junction components. The patient group, with a mean age of 49.9 years, exhibited various mitochondrial disorders including chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Patients with mitochondrial disorders had a high percentage of remodeled (p= 0.0001), neoformed (p= 0.0049) and dilated (p= 0.016) endplates. There was a trend toward an increased proportion of neuromuscular junctions with terminal Schwann cell extension in these patients (p= 0.052). No significant difference was found in myofiber diameter between the groups. The observed neuromuscular junction defects varied widely across different mitochondrial disorder phenotypes and were present even without accompanying muscle weakness or neuropathy. This suggest that mitochondrial disorders are associated with a primary NMJ remodeling independent of muscle structural damage. Pathomechanisms underpinning this remodeling of the neuromuscular junction, as well as clinical factors predictive of this remodeling, remain to be fully characterized.

Keywords: Confocal microscopy; Denervation; Fatigability; Ptosis; Reinnervation; Remodeling.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors report no competing interests relevant to the manuscript, the authors have no relevant financial or non-financial interests to disclose. Human biological samples and associated data were obtained from TTK Biobank (CRB-HCL Hospices Civils de Lyon BB-0033-00046). All tissue samples were obtained according to French Legislation and written informed consent was obtained from patients for all samples. TTK is authorized by the French Ministry of Social Affairs and Health (DC2015-2566) with transfer authorization (AC 2015-2576). The Biobank database is registered in the national data protection commission (Commission Nationale Informatique et Libertés). Funding for this work was obtained from AFM telethon through the strategic MyoNeurALP alliance, the Fondation pour la Recherche Médicale through an “équipe FRM” funding to L.S.

LinkOut - more resources