Mitochondrial dysfunction in myasthenia gravis: Exploring directions for future immunotherapy? A review

Abstract

Myasthenia gravis (MG) is an acquired autoimmune disease characterized by impaired transmission at the neuromuscular junction, primarily manifesting as fluctuating muscle weakness, fatigability, and partial paralysis. Due to its long disease course, treatment resistance, and frequent relapses, it places a significant burden on patients and their families. In recent years, advances in molecular biology have provided growing evidence that mitochondrial dysfunction impairs muscle function and affects immune cell proliferation and differentiation in patients. Mitochondria, as the cell's energy source, play a critical role in various pathological processes in MG, including oxidative stress, dynamic abnormalities, mitophagy, and mitochondrial metabolism. The role of mitochondrial dysfunction in the pathogenesis of MG has garnered increasing attention. This manuscript primarily explores mitochondrial function and abnormal morphological changes in MG, as well as mitochondrial quality control, metabolic reprogramming, and their potential mechanisms in the pathological changes of the disease. It also reviews the current status of drug therapies aimed at improving mitochondrial function. The goal is to provide novel perspectives and strategies for future mitochondrial-targeted therapies in MG.

Figure 1.

Regulation of Mitochondrial Quality Through Mitobiogenesis and Mitophagy. Mitochondria have a limited lifespan and must be constantly renewed to maintain normal function. Mitochondrial quality is tightly regulated by two fundamental, opposing mechanisms: mitobiogenesis and mitophagy. These processes respond to cellular energy demands as well as various cellular and environmental cues. The balance between mitochondrial fusion and fission is essential for both mitobiogenesis and mitophagy.

Figure 2.

Pathological changes of mitochondria in MG and possible pathogenic mechanisms. To date, research on the role of mitochondria in the pathology of MG has primarily focused on EAMG rat muscles, MG patient muscles, and immune cells. Mitochondrial alterations are a consequence of MG and involve structural changes. Mitochondria contribute to the onset and progression of MG, with mitochondrial quality control and metabolism playing critical roles. Further investigation into mitochondria could eventually uncover the upstream mechanisms behind MG pathogenesis. MG: Myasthenia gravis; EAMG: Experimental autoimmune myasthenia gravis.