Molybdenum Disulfide Structures Increase Mitochondrial Biogenesis

Researchers here report on initial in vitro studies of a novel approach to improve mitochondrial function via an increased pace of mitochondrial replication. It is typically a long road from positive results in cell culture to a viable basis for therapy, and most cell work proves to be less useful than hoped in animals, but the novelty of the approach here makes it interesting. It is certainly true that new and better ways to improve mitochondrial function in aged tissues are much needed. It is an open question as to whether a compensatory approach based on increased mitochondrial replication will be usefully beneficial in the age-damaged environment in which the function of each individual mitochondrion is degraded.

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.

Link: https://doi.org/10.1038/s41467-024-52276-8