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 (MoS<sub>2</sub>) nanoflowers with predefined atomic vacancies that are fabricated by self-assembly of individual two-dimensional MoS<sub>2</sub> nanosheets. Treatment of mammalian cells with MoS<sub>2</sub> 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<sub>2</sub> 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<sub>2</sub> nanoflowers stimulate mitochondrial function by upregulating the expression of genes required for mitochondrial biogenesis.
Authors
- Natalie M. Garza (ORCID: https://orcid.org/0000-0002-0467-5094)
- Mohammad Zulkifli (ORCID: https://orcid.org/0000-0002-9110-9508)
- Aparna Murali (ORCID: https://orcid.org/0000-0002-5250-0061)
- Harman Kaur (ORCID: https://orcid.org/0000-0002-7536-9991)
- Giriraj Lokhande (ORCID: https://orcid.org/0000-0001-8468-4187)
- Anna L. Kersey (ORCID: https://orcid.org/0000-0001-7214-0473)
- Justin Keeney (ORCID: https://orcid.org/0000-0003-1748-0971)
- Ramu Banavath (ORCID: https://orcid.org/0000-0003-2618-4365)
- Kanwar Abhay Singh (ORCID: https://orcid.org/0000-0001-9704-0495)
- Irtisha Singh (ORCID: https://orcid.org/0000-0002-9460-3587)
- Akhilesh K. Gaharwar (ORCID: https://orcid.org/0000-0002-0284-0201)
- Sagnika Ghosh (ORCID: https://orcid.org/0000-0003-2883-7008)
- Vishal M. Gohil (ORCID: https://orcid.org/0000-0002-9920-2563)
- John Soukar (ORCID: https://orcid.org/0000-0002-1175-2895)
- Hatice Ceylan Koydemir (ORCID: https://orcid.org/0000-0002-8612-5167)
- Raquel Sitcheran (ORCID: https://orcid.org/0000-0001-8916-9707)
Institutions
- Texas A&M Health Science Center (US)
- Texas A&M Engineering Experiment Station
- Texas A&M University (US)
- Bryan College (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1038/s41467-024-52276-8
- Citations
- 19
- Primary Topic
- Advanced Nanomaterials in Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 2.23
Funders
- National Science Foundation
- U.S. Department of Defense
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- High Performance Research Computing, Texas A and M University
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Dental and Craniofacial Research
- Congressionally Directed Medical Research Programs
- Division of Cancer Epidemiology and Genetics, National Cancer Institute