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Related Experiment Video

Updated: Dec 12, 2025

Author Spotlight: Unveiling Mitochondrial Function and Cellular Metabolic Adaptation in Metabolic Diseases

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Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle

Anastasia Thoma¹, Max Lyon², Nasser Al-Shanti¹

¹Musculoskeletal Science & Sports Medicine Research Centre, Department of Life Sciences, Faculty of Science & Engineering, Manchester Metropolitan University, Manchester M1 5GD, UK.

Antioxidants (Basel, Switzerland)

|August 9, 2020

Summary

Maladaptive endoplasmic reticulum (ER) stress contributes to muscle weakness in myositis. Targeting reactive oxygen species (ROS) with EUK-134 mitigated ER stress and improved mitochondrial function in skeletal muscle cells.

Keywords:

ER stress EUK-134 antioxidant mitochondria reactive oxygen species

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Area of Science:

Biochemistry
Cell Biology
Neuromuscular Diseases

Background:

Maladaptive endoplasmic reticulum (ER) stress is linked to altered reactive oxygen species (ROS) production and mitochondrial dysfunction.
These factors are implicated in the muscle weakness observed in myositis, an autoimmune neuromuscular disorder.

Purpose of the Study:

To investigate the role of ROS generation in ER stress-induced mitochondrial dysfunction in skeletal muscle.
To evaluate the therapeutic potential of the antioxidant Eukarion (EUK)-134 in mitigating these effects.

Main Methods:

An in vitro model of ER stress was established in skeletal muscle cells using tunicamycin.
Cells were treated with tunicamycin alone or in combination with EUK-134.
Key markers of ER stress, mitochondrial function (membrane potential, respiration), mitochondrial dynamics (biogenesis, fusion, fission), and ROS generation were assessed.

Main Results:

Tunicamycin induced maladaptive ER stress and significant mitochondrial dysfunction, including loss of membrane potential and impaired respiratory function.
ER stress led to ROS-mediated mitochondrial biogenesis and fusion, paradoxically increasing fragmentation and upregulating fission markers.
EUK-134 treatment ameliorated ER stress, improved mitochondrial function, and prevented increased cellular ROS generation, though mitochondrial superoxide levels remained unchanged.

Conclusions:

Targeting ROS generation with EUK-134 can counteract ER stress-induced mitochondrial dysfunction and alterations in mitochondrial dynamics.
Quenching ROS may represent a promising therapeutic strategy for muscle weakness and dysfunction associated with chronic ER stress conditions like myositis.