Title |
UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
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Published in |
Orphanet Journal of Rare Diseases, May 2022
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DOI | 10.1186/s13023-022-02331-8 |
Pubmed ID | |
Authors |
Juan M. Suárez-Rivero, Carmen J. Pastor-Maldonado, Suleva Povea-Cabello, Mónica Álvarez-Córdoba, Irene Villalón-García, Marta Talaverón-Rey, Alejandra Suárez-Carrillo, Manuel Munuera-Cabeza, Diana Reche-López, Paula Cilleros-Holgado, Rocío Piñero-Perez, José A. Sánchez-Alcázar |
Abstract |
Mitochondrial diseases represent one of the most common groups of genetic diseases. With a prevalence greater than 1 in 5000 adults, such diseases still lack effective treatment. Current therapies are purely palliative and, in most cases, insufficient. Novel approaches to compensate and, if possible, revert mitochondrial dysfunction must be developed. In this study, we tackled the issue using as a model fibroblasts from a patient bearing a mutation in the GFM1 gene, which is involved in mitochondrial protein synthesis. Mutant GFM1 fibroblasts could not survive in galactose restrictive medium for more than 3 days, making them the perfect screening platform to test several compounds. Tetracycline enabled mutant GFM1 fibroblasts survival under nutritional stress. Here we demonstrate that tetracycline upregulates the mitochondrial Unfolded Protein Response (UPRmt), a compensatory pathway regulating mitochondrial proteostasis. We additionally report that activation of UPRmt improves mutant GFM1 cellular bioenergetics and partially restores mitochondrial protein expression. Overall, we provide compelling evidence to propose the activation of intrinsic cellular compensatory mechanisms as promising therapeutic strategy for mitochondrial diseases. |
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Geographical breakdown
Country | Count | As % |
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Spain | 7 | 47% |
Unknown | 8 | 53% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 14 | 93% |
Scientists | 1 | 7% |
Mendeley readers
Geographical breakdown
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Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 6 | 38% |
Other | 2 | 13% |
Student > Bachelor | 1 | 6% |
Student > Doctoral Student | 1 | 6% |
Student > Master | 1 | 6% |
Other | 1 | 6% |
Unknown | 4 | 25% |
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Biochemistry, Genetics and Molecular Biology | 5 | 31% |
Neuroscience | 3 | 19% |
Medicine and Dentistry | 2 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
Nursing and Health Professions | 1 | 6% |
Other | 0 | 0% |
Unknown | 4 | 25% |