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Talk by Gabriele Zaffagnini

Title: "How endolysosomal super-organelles maintain proteostasis in the long-lived female germline"
Occasion: SFB - Seminar
Start: 26.06.2025 4:15 pm
Location: CellNanOs, 38/201

About the speaker: Dr. Gabriele Zaffagnini conducts research at the CECAD Research Centre, University of Cologne, Germany

Long-lived cells are highly sensitive to proteostasis decay during aging. Oocytes, the female germ cells, are very long-lived and need to remain damage-free to ensure proper embryonic development. How mammalian oocytes maintain proteostasis during their prolonged life is unknown. We have recently discovered that, in mice, oocytes sequester and degrade protein aggregates, a hallmark of impaired proteostasis, in novel “super-organelles” that we have named EndoLysosomal Vesicular Assemblies (ELVAs). ELVAs consist of clustered endosomes, lysosomes, and autophagosomes, embedded in a liquid-like proteinaceous matrix formed by RUFY1. Largely non-degradative in immature oocytes, ELVAs relocate to the oocyte periphery and activate protein degradation shortly before fertilization, thereby degrading the sequestered aggregates. Impairment of ELVA activation, as well as overexpression of aggregating proteins after ELVAs dissolution in the early embryo, result in compromised oocyte quality and impaired embryonic development. Thus, ELVAs allow correct embryogenesis by sequestering protein aggregates in the oocyte and degrading them in a timely manner. Collectively, our results define a new paradigm for proteostasis maintenance and fertility preservation in the long-lived mouse oocyte.