Abstract
BACKGROUND AND OBJECTIVE: Phosphodiesterase-5 inhibitors (PDE5i) remain the first-line treatment for erectile dysfunction (ED). However, nearly 30% of ED patients exhibit inadequate responses or intolerable side effects. Emerging evidence indicates that mitochondrial dysfunction, characterized by bioenergetic failure, oxidative stress, and apoptosis, plays a pivotal role in the pathogenesis of ED. METHODS: This review employed a systematic literature search to comprehensively synthesize evidence on mitochondrial transplantation (MT) and mitochondrial dysfunction in the context of ED. Databases searched included PubMed, Embase, and Web of Science, covering publications from January 1, 2000 to July 1, 2025. Search strategies utilized keywords such as "mitochondrial transplantation", "erectile dysfunction", "mitochondrial dysfunction", "ROS", and "apoptosis", combined with Boolean operators (e.g., "mitochondrial transplantation AND erectile dysfunction" or "mitochondrial dysfunction OR apoptosis AND ED"). KEY CONTENT AND FINDINGS: The search initially identified 1,247 abstracts, from which 289 full-text articles were retrieved and evaluated for eligibility, ultimately yielding 58 key references incorporated into this review. This review systematically examines the potential of MT as a novel therapeutic strategy in ED. In preclinical ED models, MT restored adenosine triphosphate (ATP) levels, attenuated reactive oxygen species (ROS) accumulation, inhibited apoptotic signaling, and improved erectile hemodynamics in cavernous smooth muscle cells. Furthermore, we discuss recent advancements in mitochondrial isolation techniques, delivery optimization strategies (including nanocarriers and hydrogels), and immunological safety considerations for both autologous and allogeneic transplantation. CONCLUSIONS: Although clinical translation faces challenges such as scalable production, dosage standardization, and long-term immunocompatibility, MT holds promise as a mechanism-based therapy for refractory ED, offering new insights beyond conventional hemodynamic approaches.