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<p>The orderly architecture and energy supply of mitochondria, orchestrated by proteins, are essential for oocyte maturation. Acylglycerol kinase (AGK) is known to predominantly localize to the mitochondrial membrane and regulate multiple cellular processes related to Sengers syndrome and tumorigenesis. However, the functions of AGK in the ovaries remain largely unknown. Here, we generate mice with oocyte-specific disruption of <i>Agk</i>. Ablation of <i>Agk</i> in oocytes causes ovarian atrophy characterized by the arrest of early secondary follicles and a significantly reduced number of mature follicles, ultimately leading to female sterility. Furthermore, mitochondria in <i>Agk</i>-deficient oocytes exhibit significant structural and organizational defects. The developmental competence of <i>Agk</i>-deficient oocytes is compromised with decreased mitochondrial membrane potential, reduced mtDNA copy number, impaired ATP synthesis, and elevated reactive oxygen species. Mechanistically, single-cell RNA sequencing shows that genes associated with the mitochondrial oxidative phosphorylation (OXPHOS) pathway are among the most significantly downregulated in <i>Agk-</i>disrupted oocytes. Spatial metabolomics further identifies a substantial reduction in phosphate-associated metabolites linked to the OXPHOS pathway in <i>Agk</i>-deficient oocytes. These findings demonstrate that AGK plays an essential role in oocyte development and folliculogenesis by maintaining mitochondrial function. The present study identifies AGK as a potential diagnostic marker and therapeutic target for female infertility.</p><p></p>

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Oocyte-specific acylglycerol kinase loss leads to infertility in mice via mitochondrial dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月23日

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  • Tingting Lu,
  • Yanquan Li,
  • Fanghao Guo,
  • Chunhua Tang,
  • Shiyi Zhu,
  • Jin Dong,
  • Ping Zhang,
  • Ningling Wang,
  • Wen Li,
  • Yuchuan Zhou

摘要

The orderly architecture and energy supply of mitochondria, orchestrated by proteins, are essential for oocyte maturation. Acylglycerol kinase (AGK) is known to predominantly localize to the mitochondrial membrane and regulate multiple cellular processes related to Sengers syndrome and tumorigenesis. However, the functions of AGK in the ovaries remain largely unknown. Here, we generate mice with oocyte-specific disruption of Agk. Ablation of Agk in oocytes causes ovarian atrophy characterized by the arrest of early secondary follicles and a significantly reduced number of mature follicles, ultimately leading to female sterility. Furthermore, mitochondria in Agk-deficient oocytes exhibit significant structural and organizational defects. The developmental competence of Agk-deficient oocytes is compromised with decreased mitochondrial membrane potential, reduced mtDNA copy number, impaired ATP synthesis, and elevated reactive oxygen species. Mechanistically, single-cell RNA sequencing shows that genes associated with the mitochondrial oxidative phosphorylation (OXPHOS) pathway are among the most significantly downregulated in Agk-disrupted oocytes. Spatial metabolomics further identifies a substantial reduction in phosphate-associated metabolites linked to the OXPHOS pathway in Agk-deficient oocytes. These findings demonstrate that AGK plays an essential role in oocyte development and folliculogenesis by maintaining mitochondrial function. The present study identifies AGK as a potential diagnostic marker and therapeutic target for female infertility.