The invention relates to a PDE5 inhibitor for use in the treatment and/or prevention of a medical condition associated with mitochondrial Complex V (ATP synthase) deficiency in a human subject. In embodiments, the mitochondrial Complex V deficiency comprises at least one mutation within a structural subunit gene, or within an assembly gene, of the mitochondrial Complex V (ATP synthase). In embodiments, the invention relates to PDE5 inhibitors, such as sildenafil or tadalafil, in the treatment and/or prevention of a Maternally Inherited Leigh syndrome (MILS), a Neuropathy, an Ataxia or a Retinitis Pigmentosa (NARP) syndrome, or a neurological syndrome associated with a mitochondrial Complex V deficiency. In embodiments, the invention relates to treatment of mitochondrial Complex V deficiency caused by at least one mutation in nuclear or mitochondrial DNA, preferably DNA mutations in the MT-ATP6 gene causing MILS or NARP. The invention further relates to a pharmaceutical composition comprising a PDE5 inhibitor for use in the treatment and/or prevention of a medical condition associated with mitochondrial Complex V deficiency.