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

Abstract

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. Cells 2020, 9, 399 2 of 20Mitochondria-associated ER membranes (MAMs) are tight structural contacts, also named as MERCs (mitochondria-ER contacts);~20% of the mitochondrial surface are jointly opposing and contact directly with the ER, yielding to approximately 10 and 30 nm in distance [4,5]. MAMs participate in several cellular signaling pathways, including calcium transmission, phospholipid exchange, intracellular trafficking, autophagy, ER stress, mitochondrial biogenesis, and inflammasome formation. Disturbances to MAMs lead to neurodegenerative diseases and cancer [6,7]. Our previous work reported that MAMs are abundant in both human and mouse spermatogenic cells, and contain many crucial proteins that are associated with the Piwi-interacting RNA (piRNA) pathway [8]. However, the functions of MAMs are still mysterious in spermatogenesis.In this review, 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 summarize the ultra-structure of IMC and MAMs in mouse spermatocyte, as shown in Figure 1A. We also discuss the roles of the structural components in piRNA biogenesis and propose that further s...

Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro

“…Fast metabolic changes in the germline are enabled by translational regulation [ 246 , 247 ]. This is most likely coordinated by the germ cell specific nuage, a ribonucleoprotein dense structure found in the cytoplasm [ 248 , 249 , 250 , 251 ]. This translational control allows for fast and efficient changes during spermatogenesis and can make transcriptional analysis misleading with regard to metabolic flux events.…”

A membrane-associated condensate drives paternal epigenetic inheritance inC. elegans

“…Our data suggest that mitochondria are an important vector of transport for the PEI granules, even though we cannot exclude a function for FB-MOs in this process. Interestingly, association of RNAi-related pathways with mitochondria has been described in various animals and include spermatogenic structures like pibodies, piP-bodies, chromatoid bodies and mitochondria-associated ER membranes (Wang et al, 2020). It appears that interaction with mitochondria may be used for various purposes in the context of small RNA pathways, ranging from small RNA biogenesis (Ge et al, 2019;Munafò et al, 2019) to the here identified role in transport and TEI.…”

Strategies for Targeting Gene Therapy in Cancer Cells With Tumor-Specific Promoters

“…The piRNAs are a kind of small non-coding RNA of 24-32 nucleotides in length, named this way because of their interactions with the PIWI subfamily of Argonaut proteins which exerts a transposon gene silencing effect besides other kinds of regulation such as epigenetics, gene and protein regulation, genome rearrangement, spermatogenesis, and germ stem cells maintenance (35)(36)(37). The piRNAs can be mainly involved in epigenetic regulation rather than post-transcriptional regulation of many biological phenomena such as cancer (38,39).…”