Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction.