Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis

Diminished mitochondrial function underlies many rare inborn errors of energy metabolism and contributes to more common age-associated metabolic and neurodegenerative disorders. Thus, boosting mitochondrial biogenesis has been proposed as a potential therapeutic approach for these diseases; however, currently we have a limited arsenal of compounds that can stimulate mitochondrial function. In this study, we designed molybdenum disulfide (MoS₂) nanoflowers with predefined atomic vacancies that are fabricated by self-assembly of individual two-dimensional MoS₂ nanosheets. Treatment of mammalian cells with MoS₂ nanoflowers increased mitochondrial biogenesis by induction of PGC-1α and TFAM, which resulted in increased mitochondrial DNA copy number, enhanced expression of nuclear and mitochondrial-DNA encoded genes, and increased levels of mitochondrial respiratory chain proteins. Consistent with increased mitochondrial biogenesis, treatment with MoS₂ nanoflowers enhanced mitochondrial respiratory capacity and adenosine triphosphate production in multiple mammalian cell types. Taken together, this study reveals that predefined atomic vacancies in MoS₂ nanoflowers stimulate mitochondrial function by upregulating the expression of genes required for mitochondrial biogenesis.