Work

Mitochondrial proteins contribute to the pathogenesis of myasthenia gravis

Year: 2025

Type: article

Abstract: Myasthenia gravis (MG) is an autoimmune disorder mediated by B-cells, characterized by muscle weakness and fatigue. Mitochondria, essential for energy production and muscle function, have been implicated in MG. Despite their importance, the exact relationship between mitochondrial proteins (MPs) and MG remains unclear. This study utilized two-sample Mendelian Randomization (TSMR) to investigate potential causal associations between MPs and MG. Data from the largest available genome-wide associated study (GWAS), comprising 1873 acetylcholine receptor (AchR) antibody-positive MG patients (1278 late-onset MG [LOMG] and 595 early-onset MG [EOMG]), were analyzed. A total of 66 MPs were selected as exposure variables, with MG and its subtypes as outcomes. Analyses employed inverse variance weighted (IVW), MR-PRESSO, MR-Egger, and weighted median methods, with heterogeneity assessed using Cochran's Q statistic. Significant causal associations were found between MPs and MG subtypes. For LOMG, GrpE protein homolog 1, oligoribonuclease, protein SCO1 homolog, and rRNA methyltransferase 3 were linked to increased risk. Cytochrome c oxidase subunit 7A1 was associated with higher EOMG risk, while [pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, dihydrolipoyl dehydrogenase, and NFU1 iron-sulfur cluster scaffold were linked to reduced EOMG risk. MPs such as dihydrolipoyl dehydrogenase and NAD-dependent protein deacylase sirtuin-5 showed protective effects against MG, while GrpE protein homolog 1, mitochondrial glutamate carrier 2, oligoribonuclease, and protein SCO1 homolog were associated with increased risk. This MR analysis suggests potential causal relationships between MPs and MG, highlighting the need for further research to validate these findings and explore the mechanisms underlying these associations.

Source: Scientific Reports

DOI: 10.1038/s41598-025-22607-w