Molybdenum disulfide boosts mitochondrial biogenesis

Introduction to mitochondrial biogenesis

Mitochondria are essential for cellular energy production, generating adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). Defects in mitochondrial function are linked to various metabolic and neurodegenerative disorders. Enhancing mitochondrial biogenesis is a promising therapeutic strategy for these conditions.

Role of molybdenum disulfide

Recent studies have explored the use of molybdenum disulfide (MoS2) nanoparticles to stimulate mitochondrial biogenesis. MoS2 nanoflowers, designed with predefined atomic vacancies, have shown potential in boosting mitochondrial function by upregulating key genes involved in mitochondrial biogenesis.

Mechanism of action

MoS2 nanoflowers increase mitochondrial biogenesis by inducing the expression of PGC-1α and TFAM, leading to higher mitochondrial DNA copy numbers and enhanced expression of nuclear and mitochondrial-DNA encoded genes. This results in increased levels of mitochondrial respiratory chain proteins, enhancing mitochondrial respiratory capacity and ATP production.

Synthesis and characterization

MoS2 nanoflowers are synthesized using molecular precursors of molybdenum and sulfur in a hydrothermal process. The resulting nanoflowers are characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD) to confirm their hexagonal crystal structure and the presence of atomic vacancies.

Cellular compatibility

Studies have shown that MoS2 nanoflowers are highly cytocompatible, with no significant impact on cell viability at concentrations up to 200 μg/mL. The nanoflowers are internalized by cells and localize within endosomal vesicles, as confirmed by TEM and fluorescence imaging.

Transcriptomic analysis

RNA sequencing of human mesenchymal stem cells (hMSCs) treated with MoS2 nanoflowers revealed significant changes in gene expression profiles. High atomic vacancy MoS2 nanoflowers upregulated genes involved in mitochondrial electron transport and ATP synthesis, indicating enhanced mitochondrial biogenesis.

Impact on mitochondrial function

MoS2 nanoflowers with high atomic vacancies increased mitochondrial DNA copy number and the expression of mitochondrial proteins. This led to enhanced mitochondrial respiration and ATP production, as confirmed by Seahorse XF24 assay and Western blot analysis.

Reduction of oxidative stress

MoS2 nanoflowers also reduced cellular and mitochondrial reactive oxygen species (ROS) levels, further supporting their role in enhancing mitochondrial function. The reduction in ROS levels is attributed to the catalytic activity of MoS2 nanoflowers and the activation of antioxidant genes.

Conclusion

MoS2 nanoflowers with high atomic vacancies represent a promising approach for enhancing mitochondrial biogenesis and function. By reducing oxidative stress and upregulating key mitochondrial genes, these nanoflowers could serve as a potential therapeutic for metabolic and neurodegenerative disorders.

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