Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast
Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast
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DOI：
10.1073/pnas.0911055107
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发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Yanagida, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Takeda, Kojiro;Yoshida, Tomoko;Yanagida, Mitsuhiro
对营养提示的增殖和静止的调节对于医学和基础生物学是重要的。裂殖酵母裂殖酵母作为一个模型，由于响应低氮源的增殖细胞转移到代谢活性的静止期（以下称为G0期）。S.粟酒酵母G0期细胞可存活数月而不生长和分裂。氮补充恢复营养增殖阶段（指定VEG）。约40个基因所需的G0的维护被确定，但更多的仍然有待确定。我们在这里显示，使用突变体，蛋白酶体是维持G0静止所必需的。蛋白酶体在G0期和VEG期的功能结果似乎是不同的。在蛋白酶体功能障碍时，产生许多抗氧化蛋白和响应ROS（活性氧）的化合物。此外，发生线粒体的自噬介导的破坏，其通过消除产生ROS的线粒体来抑制活力的丧失。这些防御反应在G0期出现，而在VEG中没有，表明蛋白酶体在G0期稳态中的主要功能是最小化ROS。因此，蛋白酶体和自噬协同支持S.粟酒G0期。
Regulations of proliferation and quiescence in response to nutritional cues are important for medicine and basic biology. The fission yeast Schizosaccharomyces pombe serves as a model, owing to the shift of proliferating cells to the metabolically active quiescence (designate G0 phase hereafter) by responding to low nitrogen source. S. pombe G0 phase cells keep alive for months without growth and division. Nitrogen replenishment reinstates vegetative proliferation phase (designate VEG). Some 40 genes required for G0 maintenance were identified, but many more remain to be identified. We here show, using mutants, that the proteasome is required for maintaining G0 quiescence. Functional outcomes of proteasome in G0 and VEG phases appear to be distinct. Upon proteasome dysfunction, a number of antioxidant proteins and compounds responsive to ROS (reactive oxygen species) are produced. In addition, autophagy-mediated destruction of mitochondria occurs, which suppresses the loss of viability by eliminating ROS-generating mitochondria. These defensive responses are found in G0 but not in VEG, suggesting that the main function of proteasome in G0 phase homeostasis is to minimize ROS. Proteasome and autophagy are thus collaborative to support the lifespan of S. pombe G0 phase.