Duchenne Muscular Dystrophy (DMD) is a complex disorder characterized by the lack of dystrophin, a protein fundamental to maintaining muscle integrity during contraction. While remarkable progress has been made in genetic approaches to restore dystrophin, or its function, targeting secondary pathological mechanisms remains an important issue to improve the efficacy of therapeutic interventions. Muscle weakness in DMD is thought to be dependent, at least in part, on damaged mitochondria and compromised bioenergetics. Mitochondrial impairment is one of the earliest dysfunction of dystrophic muscle but despite this few studies have explored the impact of altered mitochondrial dynamics in DMD. The overall goal of my research is to establish how mitochondrial fission/fusion can contribute to muscle wasting in DMD and attempt innovative strategies to target them improving dystrophic phenotype. Besides in DMD, fibers become vulnerable to contraction-induced damage and undergo cycles of necrosis and regeneration, leading to progressive deficiency of satellite cells (SC) pool and the persistent activation of the fibro/adipogenic progenitors (FAP) fueling fat and fibrotic tissue replacement inside the muscle. The interplay between SC and FAP finely orchestrates skeletal muscle homeostasis regulating muscle regeneration and both populations reveal metabolic and mitochondrial alterations in DMD. Consistently, the modulation of muscle progenitor cells’ metabolism is emerging as a pivotal mechanism to counteract DMD dysfunctions. Another important topic of my research is to identify an effective metabolic enhancer drug to promote metabolic rewiring of dystrophic muscle and stem cells populations increasing regeneration and slowing down muscle degeneration.