Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis.
Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis.
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DOI：
10.18632/aging.100547
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Titorenko VI
中科院分区：
文献类型：
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作者：
Richard VR;Leonov A;Beach A;Burstein MT;Koupaki O;Gomez-Perez A;Levy S;Pluska L;Mattie S;Rafesh R;Iouk T;Sheibani S;Greenwood M;Vali H;Titorenko VI
大线粒体自噬控制线粒体的质量和数量。它涉及将功能失调或过多的线粒体隔离在双膜自噬体中，然后与液泡/溶酶体融合以递送这些线粒体进行降解。为了研究巨线粒体自噬在酵母中的生理作用，我们研究了该过程的 atg32Δ 依赖性突变块如何影响在含有低浓度 (0.2%) 葡萄糖的营养丰富的培养基中生长的细胞的时间寿命。在热量限制（CR）的这些延长寿命的条件下，酵母细胞不会挨饿。我们还评估了巨线粒体自噬在石胆酸 (LCA) 寿命延长中的作用，石胆酸是一种胆汁酸，可在 CR 条件下延长酵母寿命。我们的研究结果表明，巨线粒体自噬是一种长寿保证过程，是 CR 和 LCA 对酵母寿命产生协同有益作用的基础。我们对 atg32Δ 突变如何影响线粒体形态、组成和功能的分析表明，巨线粒体自噬是维持健康线粒体网络所必需的。我们对野生型和 atg32Δ 细胞纯化的细胞器膜脂质组的比较分析表明，巨线粒体自噬是维持细胞脂质稳态所必需的。我们得出的结论是，巨线粒体自噬通过调节线粒体内外的重要细胞过程来定义酵母的寿命。
Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how the atg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria.