在酵母溶酶样真空体中的V-ATPase分解是复制性衰老中溶酶功能障碍的表型驱动因素
Fiza Hashmi1, Patricia M Kane1
1Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY USA.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
随着年龄的增长,由于V-ATPase分解,溶解体酸性减弱. 卡路里限制和维护RAVE复合体水平可以防止这种情况,保护细胞功能并延长酵母的寿命.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 分子机制的分子机制
背景情况:
- 在不同物种中,随着年龄的增长,溶酶体酸化和功能下降.
- V-ATPases对于有机细胞酸化至关重要,它们的活性通过可逆分解来调节.
- 酵母菌 (Saccharomyces cerevisiae) 作为研究细胞衰老的模型.
研究的目的:
- 调查V-ATPase分解在酵母复制老化中的作用.
- 探索卡路里限制对衰老过程中V-ATPase功能的影响.
- 为了确定调节V-ATPase组装和拆卸在衰老细胞中的因素.
主要方法:
- 使用酵母*Saccharomyces cerevisiae*作为一个复制老化模型.
- 在老化细胞中观察到V-ATPase分解为V1和V0亚复合体.
- 评估了热量限制和基因操纵 (RAVE复合物,Oxr1) 对V-ATPase和真空 pH 的影响.
主要成果:
- 在老化的酵母细胞 (≥5个分裂) 中,V-ATPases分解,导致真空的化.
- 热量限制可以防止V-ATPase分解,并保持老细胞中真空 pH 恒温.
- RAVE复合物促进组装,而Oxr1促进拆卸;这些因素的突变会影响寿命. 拉维2水平随着年龄的增长而下降,其过度表达延迟了拆卸.
结论:
- 减少V-ATPase组合有助于与年龄相关的溶酶体酸化损失.
- V-ATPase分解是酵母复制寿命的一个关键因素.
- 准V-ATPase组合可能为抵消与年龄相关的细胞功能障碍提供策略.
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