Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis

• Published in: Nature communications 2024-09, Vol.15 (1), p.8136-15, Article 8136
• Main Authors: Singh, Kanwar Abhay, Soukar, John, Zulkifli, Mohammad, Kersey, Anna, Lokhande, Giriraj, Ghosh, Sagnika, Murali, Aparna, Garza, Natalie M., Kaur, Harman, Keeney, Justin N., Banavath, Ramu, Ceylan Koydemir, Hatice, Sitcheran, Raquel, Singh, Irtisha, Gohil, Vishal M., Gaharwar, Akhilesh K.
• Format: Article
• Language: English
• Subjects: 13/106; 13/31; 147/135; 147/143; 38/77; 38/91; 639/301/357/1018; 639/301/54/2295; 639/925/350/354; 82/80; Adenosine triphosphate; Adenosine Triphosphate - metabolism; Age; Age related diseases; Animals; Atomic properties; ATP; Biosynthesis; Copy number; Deoxyribonucleic acid; Disulfides - chemistry; DNA; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Electron transport; Energy metabolism; Gene expression; Genes; Genetic disorders; Humanities and Social Sciences; Humans; Inborn errors of metabolism; Mammalian cells; Mammals; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Molybdenum; Molybdenum - chemistry; Molybdenum - metabolism; Molybdenum - pharmacology; Molybdenum disulfide; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Neurodegenerative diseases; Organelle Biogenesis; Pharmacology; Rare diseases; Reactive oxygen species; Science; Science (multidisciplinary); Self-assembly
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52276-8

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 (MoS 2 ) nanoflowers with predefined atomic vacancies that are fabricated by self-assembly of individual two-dimensional MoS 2 nanosheets. Treatment of mammalian cells with MoS 2 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 MoS 2 nanoflowers enhanced mitochondrial respiratory capacity and adenosine triphosphate production in multiple mammalian cell types. Taken together, this study reveals that predefined atomic vacancies in MoS 2 nanoflowers stimulate mitochondrial function by upregulating the expression of genes required for mitochondrial biogenesis. Mitochondrial dysfunction is linked to various rare genetic disorders and common age-related diseases, but few compounds can stimulate mitochondrial activity. Here, the authors address this issue by developing atomic vacancy-rich molybdenum disulfide nanoparticles that can catalyze intracellular reactive oxygen species to enhance mitochondrial biogenesis and cellular respiration.