Mitochondrial dynamics and biogenesis indicators may serve as potential biomarkers for diagnosis of myasthenia gravis

Abstract

Due to challenges in diagnosing myasthenia gravis (MG), identifying novel diagnostic biomarkers for this disease is essential. Mitochondria are key organelles that regulate multiple physiological functions, such as energy production, cell proliferation and cell death. In the present study, Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were compared between patients with MG and healthy subjects to identify potential diagnostic biomarkers for MG. Blood samples were collected from 50 patients with MG and 50 healthy subjects. The participants' demographic information and routine blood test results were recorded. Mitochondrial dynamics were evaluated and levels of Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were determined in peripheral blood mononuclear cells using western blotting and reverse transcription-quantitative PCR, respectively. Receiver operating characteristic curve analysis was used to evaluate the diagnostic accuracy of these indicators. The areas under the curve values of Mfn1/2, Opa1, Drp1, Fis1,AMPK, PGC-1α, NRF-1 and TFAM were 0.5408-0.8696. Compared with control subjects, mRNA expression levels of Mfn1/2, Opa1, AMPK, PGC-1α, NRF-1 and TFAM were lower, while those of Drp1 and Fis1 were higher in patients with MG. The protein expression levels of all these molecules were lower in patients with MG than in control subjects. These results suggested that mitochondrial dynamics and biogenesis indicators may be diagnostic biomarkers for MG.

Skeletal Muscle Mitochondrial Dysfunction Mediated byPseudomonas aeruginosaQuorum Sensing Transcription Factor MvfR: Reversing Effects with Anti-MvfR and Mitochondrial-Targeted Compounds

“…Damaged mitochondria are removed by mitophagy (49). Given that our results show that MvfR negatively impacts mitochondrial homeostasis, we investigated whether mitophagy was affected in the skeletal muscle of infected mice.…”

“…Both D88 and SS-31 reinstated the levels of these proteins in the PA14-infected muscle tissues to similar levels as observed in the ∆mvfR or control group, with SS-31 promoting a slightly higher increase in MFN1 (Figure 3B). Damaged mitochondria are removed by mitophagy (49). Given that our results show that MvfR negatively impacts mitochondrial homeostasis, we investigated whether mitophagy was affected in the skeletal muscle of infected mice.…”

“…Mitochondrial fission is crucial for several processes, including proper distribution of mitochondria, cytochrome C release, and mitophagy (48). Mitochondrial fission protein 1 (FIS1) is one of the adaptor proteins involved in mitochondrial fission and the recruitment of the dynamin-related protein 1 (DRP1), a cytosolic GTPase protein, to the mitochondrial outer membrane (48)(49)(50). We assessed whether MvfR impacts the levels of these proteins using the mitochondrial lysates of the skeletal muscle from the infected mice (Figure 3A).…”

Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics

“…Regardless, it seems like the dysregulation of organelle division processes may be a common feature seen in a wide variety of pathological conditions, whether directly or indirectly. Indeed, an increase in DRP1 and FIS1 mRNA but a decrease in their protein levels in peripheral blood mononuclear cells isolated from blood samples is reproducibly seen in patients with the autoimmune disorder myasthenia gravis, prompting the proposal to use these as biomarkers for this disease [ 193 ]. Altogether, this raises the possibility that modulating organelle fission may be a future broad-spectrum treatment to improve cell performance and organelle function in a host of conditions.…”

Overview of biomarkers in myasthenia gravis

“…Mitochondrial proteins as energy expenditure markers could be helpful in MG diagnosis. Mitofusin 1, and 2, optic atrophy type 1, dynamin-related protein 1 and fission 1, adenosine monophosphate (AMP)-activated protein kinase, PPAR γ co-activator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A are reduced in MG patients [106]. Low plasma vitronectin level is another diagnostic biomarker in MG. Vitronectin is a glycoprotein in blood and the extracellular matrix which induces complement-dependent immune response and clot regulation.…”