| PubMedID | 39690163 |
|---|---|
| タイトル | Macronucleophagy maintains cell viability under nitrogen starvation by modulating micronucleophagy. |
| ジャーナル | Nature communications 2024 Dec;15(1):10670. |
| 著者 | Li Z, Mochida K, Nakatogawa H |
- 研究員
- Posted by 東京科学大学 総合研究院細胞制御工学研究センター Ziyang Li
- 投稿日 2024/12/18
Let me briefly introduce our recent work published in Nature Communications.
In Saccharomyces cerevisiae, two nucleophagy pathways have been identified: micronucleophagy (also known as piecemeal microautophagy of the nucleus) and macronucleophagy. Micronucleophagy involves invagination of the vacuolar membrane at nucleus-vacuole junctions (NVJs), which are formed through the interaction between Nvj1 and Vac8. On the other hand, macronucleophagy, which depends on the autophagy receptor Atg39, sequesters nucleus-derived vesicles into autophagosomes.
In our previous study, we demonstrated that deletion of the macronucleophagy receptor ATG39, which abolishes macronucleophagy, significantly reduces cell viability during prolonged nitrogen starvation. However, the mechanism by which nucleophagy impacts cell viability under such conditions remained unclear.
In this study, we found that Nvj1-dependent micronucleophagy is enhanced in macronucleophagy-defective atg39 mutants, actively transporting various nuclear components into the vacuole during prolonged nitrogen starvation. We also observed that Nvj1 is degraded via Atg39-dependent macronucleophagy. In the absence of macronucleophagy, Nvj1 accumulates on the nuclear membrane, which contributes to the enhancement of micronucleophagy. Furthermore, the cell death observed in macronucleophagy-defective cells was almost completely suppressed by blocking micronucleophagy, suggesting that excessive removal of nuclear components through enhanced micronucleophagy may disrupt normal nuclear processes, ultimately leading to cell death.
From this work, we discovered that macronucleophagy regulates micronucleophagy by mediating the degradation of Nvj1, suggesting an intriguing cross-talk between the two nucleophagy pathways. Moreover, we propose that uncontrolled micronucleophagy can be lethal for yeast cells. Although we are still far from fully understanding how enhanced micronucleophagy is linked to cell death, we hope this study serves as a steppingstone toward uncovering the physiological significance of nucleophagy.
We faced two major rounds of revisions before publication. Initially, our manuscript was reviewed by three referees, with two of them co-reviewing as part of Nature Communications’ initiative to train peer reviewers. Unfortunately, these two referees did not support our first revision, citing reasons that were more emotional than scientific. Consequently, an arbitrating referee was assigned to evaluate our work. Thankfully, this referee was supportive, allowing us to proceed to publication.
Finally, I would like to express my heartfelt gratitude to Prof. Hitoshi Nakatogawa and Dr. Keisuke Mochida, who provided invaluable feedback at every stage of this research.