| First Author | Jain IH | Year | 2016 |
| Journal | Science | Volume | 352 |
| Issue | 6281 | Pages | 54-61 |
| PubMed ID | 26917594 | Mgi Jnum | J:231513 |
| Mgi Id | MGI:5771703 | Doi | 10.1126/science.aad9642 |
| Citation | Jain IH, et al. (2016) Hypoxia as a therapy for mitochondrial disease. Science 352(6281):54-61 |
| abstractText | Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction. |
