Hasan Md Mahmudul, Goto Shinji, Sekiya Reiko, Hayashi Toshinori, Li Tao-Sheng, Kawabata Tsuyoshi
Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
Life Sci Alliance. 2025 Feb 4;8(4). doi: 10.26508/lsa.202402772. Print 2025 Apr.
Salamanders demonstrate exceptional resistance to starvation, allowing them to endure extended periods without food in their natural habitats. Although autophagy, a process involving evolutionarily conserved proteins, promotes survival during food scarcity, the specific mechanism by which it contributes to the extreme starvation resistance in newt cells remains unexplored. Our study, using the newt species , reveals that newt primary fibroblasts maintain constant autophagy activation during prolonged cellular starvation. Unlike normal mammalian fibroblasts, where autophagosome formation increases during acute starvation but returns to baseline levels after extended periods, newt cells maintain elevated autophagosome numbers even 4 d after autophagy initiation, surpassing levels observed in nutrient-rich conditions. Unique mTOR orthologs show reduced lysosomal localization compared with mammalian cells in both nutrient-rich and starved states. However, newt cells exhibit dephosphorylation of mTOR substrates under starvation conditions, similar to mammalian cells. These observations suggest that newts may have evolved a distinctive system to balance seemingly conflicting factors: high regenerative capacity and autophagy-mediated survival during starvation.
蝾螈对饥饿表现出极强的抵抗力，这使它们能够在自然栖息地中长时间不进食。尽管自噬（一个涉及进化上保守蛋白质的过程）在食物短缺时促进生存，但它有助于蝾螈细胞极端抗饥饿能力的具体机制仍未被探索。我们使用蝾螈物种进行的研究表明，蝾螈原代成纤维细胞在长时间细胞饥饿期间保持持续的自噬激活。与正常哺乳动物成纤维细胞不同，在急性饥饿期间自噬体形成增加，但在长时间后会恢复到基线水平，蝾螈细胞即使在自噬启动4天后自噬体数量仍保持升高，超过在营养丰富条件下观察到的水平。独特的mTOR直系同源物在营养丰富和饥饿状态下与哺乳动物细胞相比，溶酶体定位都减少。然而，蝾螈细胞在饥饿条件下表现出mTOR底物的去磷酸化，这与哺乳动物细胞类似。这些观察结果表明，蝾螈可能已经进化出一种独特的系统来平衡看似相互矛盾的因素：高再生能力和饥饿期间自噬介导的生存能力。
