PIWI proteins tether the piRNA biogenesis machinery to mitochondria during mammalian spermatogenesis.

ABSTRACT: piRNA biogenesis occurs in the intermitochondrial cement (IMC) in mammalian germ cells. The mechanisms by which IMC components engage mitochondria to form an efficient piRNA biogenesis machinery remain elusive. Here, we demonstrate that PIWI proteins orchestrate the assembly and disassembly of the piRNA biogenesis machinery in mice. The mitochondrial-anchored protein ASZ1 specifically interacts with PIWIL2 and recruits PIWIL2 to IMC granules. Sequentially, piRNAs competitively bind PIWIL2, leading to ASZ1-PIWIL2 dissociation. In fetal male germ cells, ASZ1-PIWIL2-TDRD1 forms a seed complex to initiate the assembly of the piRNA biogenesis machinery. During postnatal meiosis, the TDRKH-PIWIL1-TDRD1 complex synergizes with the ASZ1-PIWIL2-TDRD1 complex to induce substantial IMC assembly and p

SUBMITTER: Gao J 

PROVIDER: S-EPMC12624062 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature