Nat Rev Urol 2025 Nov 11; doi: 10.1038/s41585-025-01109-4.

Sperm mitochondrial sheath formation - how and why?

???displayArticle.abstract???
The sperm tail is a modified motile cilium analogous to those found in tissues including the lung and brain. They have been evolutionarily sculpted to optimize motility and, therefore, fertility, through the dynamic and challenging environment of the female reproductive tract. Sperm tails are composed of three structurally distinct regions: the midpiece, the principal piece and the end piece. The most proximal region - the midpiece - is surrounded by a mitochondrial sheath, which has been proposed to provide structural integrity and ATP as fuel for sperm tail movement. Despite the main phases of mitochondrial sheath assembly being described, the specific biological mechanisms that underpin its formation and maturation remain poorly defined and, in many cases, unknown. Moreover, emerging evidence has highlighted that the precise contribution of the mitochondrial sheath to energy production in sperm has been misunderstood. ATP generation via glycolysis and mitochondrial respiration, previously believed to be physically uncoupled, engage in crosstalk to maximize sperm function, competition and overall fertility. Understanding these processes could not only provide vital insights into the aetiology of male infertility and offer targets for contraceptive development but could also provide insights into mechanisms of relevance to other tissues in which mitochondrial dynamics is challenging to monitor.

???displayArticle.pubmedLink??? 41219388
???displayArticle.link??? Nat Rev Urol