| First Author | Pambianco S | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 11 | Pages | 3010-3023 |
| PubMed ID | 27974213 | Mgi Jnum | J:241707 |
| Mgi Id | MGI:5903534 | Doi | 10.1016/j.celrep.2016.11.044 |
| Citation | Pambianco S, et al. (2016) Reversal of Defective Mitochondrial Biogenesis in Limb-Girdle Muscular Dystrophy 2D by Independent Modulation of Histone and PGC-1alpha Acetylation. Cell Rep 17(11):3010-3023 |
| abstractText | Mitochondrial dysfunction occurs in many muscle degenerative disorders. Here, we demonstrate that mitochondrial biogenesis was impaired in limb-girdle muscular dystrophy (LGMD) 2D patients and mice and was associated with impaired OxPhos capacity. Two distinct approaches that modulated histones or peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) acetylation exerted equivalent functional effects by targeting different mitochondrial pathways (mitochondrial biogenesis or fatty acid oxidation[FAO]). The histone deacetylase inhibitor Trichostatin A (TSA) changed chromatin assembly at the PGC-1alpha promoter, restored mitochondrial biogenesis, and enhanced muscle oxidative capacity. Conversely, nitric oxide (NO) triggered post translation modifications of PGC-1alpha and induced FAO, recovering the bioenergetics impairment of muscles but shunting the defective mitochondrial biogenesis. In conclusion, a transcriptional blockade of mitochondrial biogenesis occurred in LGMD-2D and could be recovered by TSA changing chromatin conformation, or it could be overcome by NO activating a mitochondrial salvage pathway. |
