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Comments on Fujita, T. et al. (2019) International Worm Meeting "Identification of novel autophagy negative regulator modulating C. elegans reproductive lifespan." (0)
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Fujita, T., Kubo, S., Hamasaki, M., Ogawa, H., Nakamura, S., & Yoshimori, T. (2019). Identification of novel autophagy negative regulator modulating C. elegans reproductive lifespan presented in International Worm Meeting. Unpublished information; cite only with author permission.
In many species reproductive capacity is negatively correlated with animal lifespan. How the balance between these two is regulated is still unclear. The knowledge regarding the factors or processes specifically regulating reproductive capacity are still limited. So far it has been shown that TGF-b Sma/Mab signaling pathway non-cell autonomously regulates reproductive lifespan (Luo et al., Cell, 2010) but the gonad intrinsic factor is not poorly characterized. By using siRNA based screening in mammalian cell culture we identified novel nuclear protein, which negatively regulates an evolutionally conserved cytoplasmic degradation process, autophagy. Knockdown of the protein function induced autophagy via transcriptional upregulation of some autophagy related genes. The expression study of C. elegans homologs revealed that this nuclear protein is highly expressed in germline and/ or somatic gonadal cells including distal tip cells and sheath cells. Moreover, knockdown of these protein function significantly extended reproductive lifespan in an autophagy dependent manner, but not extended animal lifespan. These results indicate that this novel autophagy negative regulators uncouple the balance between reproduction and animal lifespan and thus are key factors to elucidate the underlying mechanism. We would like to discuss the possible mechanisms with our updated data.
Affiliation:
- Graduate School of Medicine, Osaka University, Osaka, JP