Pambianco 2016 Cell Rep

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Pambianco S, Giovarelli M, Perrotta C, Zecchini S, Cervia D3, Di Renzo I, Moscheni C, Ripolone M, Violano R, Moggio M, Bassi MT, Puri PL, Latella L, Clementi E, De Palma C (2016) Reversal of defective mitochondrial biogenesis in limb-girdle muscular dystrophy 2D by independent modulation of histone and PGC-1α acetylation. Cell Rep 17:3010-23.

» PMID: 27974213 Open Access

Pambianco S, Giovarelli M, Perrotta C, Zecchini S, Cervia D3, Di Renzo I, Moscheni C, Ripolone M, Violano R, Moggio M, Bassi MT, Puri PL, Latella L, Clementi E, De Palma C (2016) Cell Rep

Abstract: 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 α (PGC-1α) 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-1α promoter, restored mitochondrial biogenesis, and enhanced muscle oxidative capacity. Conversely, nitric oxide (NO) triggered post translation modifications of PGC-1α 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.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.


O2k-Network Lab: IT Milan Clementi E


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, Genetic knockout;overexpression  Pathology: Other 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells, Permeabilized tissue, Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k