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Updated: Jun 3, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline
Toshiaki Watanabe1, Shinichiro Chuma, Yasuhiro Yamamoto
1Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, 411-8540, Japan. toshiaki.watanabe@yale.edu
Abstract:
MITOPLD is a member of the phospholipase D superfamily proteins conserved among diverse species. Zucchini (Zuc), the Drosophila homolog of MITOPLD, has been implicated in primary biogenesis of Piwi-interacting RNAs (piRNAs). By contrast, MITOPLD has been shown to hydrolyze cardiolipin in the outer membrane of mitochondria to generate phosphatidic acid, which is a signaling molecule. To assess whether the mammalian MITOPLD is involved in piRNA biogenesis, we generated Mitopld mutant mice. The mice display meiotic arrest during spermatogenesis, demethylation and derepression of retrotransposons, and defects in primary piRNA biogenesis. Furthermore, in mutant germ cells, mitochondria and the components of the nuage, a perinuclear structure involved in piRNA biogenesis/function, are mislocalized to regions around the centrosome, suggesting that MITOPLD may be involved in microtubule-dependent localization of mitochondria and these proteins. Our results indicate a conserved role for MITOPLD/Zuc in the piRNA pathway and link mitochondrial membrane metabolism/signaling to small RNA biogenesis.
Insights
Mammalian MITOPLD is crucial for piRNA biogenesis and spermatogenesis. Mutant mice show meiotic arrest and defects in small RNA pathways, linking mitochondria to piRNA production.
Area of Science:
- Mitochondrial biology
- RNA biology
- Reproductive biology
Background:
- MITOPLD, a phospholipase D superfamily protein, hydrolyzes cardiolipin in mitochondria.
- Its Drosophila homolog, Zucchini (Zuc), is involved in piRNA biogenesis.
- The role of mammalian MITOPLD in piRNA pathway remains unclear.
Purpose of the Study:
- To investigate the role of mammalian MITOPLD in piRNA biogenesis and spermatogenesis.
- To determine if MITOPLD links mitochondrial function to small RNA pathways.
Main Methods:
- Generation and analysis of Mitopld mutant mice.
- Assessment of meiotic progression, retrotransposon activity, and piRNA biogenesis.
- Microscopic analysis of germ cell mitochondria and nuage components.
Main Results:
- Mitopld mutant mice exhibit meiotic arrest during spermatogenesis.
- Mutant mice show retrotransposon demethylation and derepression.
- Defects in primary piRNA biogenesis were observed in mutant germ cells.
- Mitochondria and nuage components are mislocalized around the centrosome in mutant germ cells.
Conclusions:
- Mammalian MITOPLD plays a conserved role in the piRNA pathway.
- MITOPLD is essential for spermatogenesis and maintaining genome integrity via piRNA regulation.
- The study links mitochondrial metabolism and signaling to small RNA biogenesis.
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