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In this review, we discuss the underlying mechanisms causing mitochondrial dysfunction in ischemic skeletal muscle, including causal evidence in rodent studies, and highlight emerging mitochondrial-targeted therapies that have potential to improve PAD outcomes. Particularly, we will analyze literature data on reactive oxygen species production and potential counteracting endogenous and exogenous antioxidants.Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here,