Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan.
Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan.
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DOI：
10.1007/s11357-023-00796-4
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发表时间：
2023-08
期刊：
影响因子：
5.6
通讯作者：
Kaya, Alaattin
中科院分区：
文献类型：
--
作者：
Phua, Cheryl Zi Jin;Zhao, Xiaqing;Turcios-Hernandez, Lesly;McKernan, Morrigan;Abyadeh, Morteza;Ma, Siming;Promislow, Daniel;Kaeberlein, Matt;Kaya, Alaattin
线粒体功能的改变与寿命调节密切相关，但潜在的机制仍不清楚。在这里，我们报告了 167 个酵母敲除菌株的时间顺序和复制寿命差异，每个菌株都缺乏单个核编码线粒体基因，其中包括 144 个与人类同源的基因，其中许多与疾病相关。我们通过分析发酵和呼吸培养条件下每个菌株的蛋白质组、脂质组和代谢组的概况，剖析了观察到的寿命差异的特征，它们分别对应于复制细胞和按时间顺序衰老细胞的代谢状态。对延长寿命表型、蛋白质和代谢物水平之间关系的检查表明，尽管许多核编码线粒体基因执行不同的功能，但它们的抑制削弱了控制胞浆核糖体蛋白质丰度、肌动蛋白动力学和蛋白酶体功能以调节寿命的共同机制。通过这项工作学到的寿命控制原理可能适用于更复杂生物体的寿命调节，因为线粒体功能的许多方面在真核生物中高度保守。在线版本包含可在 10.1007/s11357-023-00796-4 获取的补充材料。
Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain’s proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes. The online version contains supplementary material available at 10.1007/s11357-023-00796-4.
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影响因子：
4.5
作者：
Fabrizio P;Hoon S;Shamalnasab M;Galbani A;Wei M;Giaever G;Nislow C;Longo VD
通讯作者：
Longo VD
影响因子：
3.9
作者：
Delaney, Joe R.;Murakami, Christopher;Chou, Annie;Carr, Daniel;Schleit, Jennifer;Sutphin, George L.;An, Elroy H.;Castanza, Anthony S.;Fletcher, Marissa;Goswami, Sarani;Higgins, Sean;Holmberg, Mollie;Hui, Jessica;Jelic, Monika;Jeong, Ki-Soo;Kim, Jin R.;Klum, Shannon;Liao, Eric;Lin, Michael S.;Lo, Winston;Miller, Hillary;Moller, Richard;Peng, Zhao J.;Pollard, Tom;Pradeep, Prarthana;Pruett, Dillon;Rai, Dilreet;Ros, Vanessa;Schuster, Alex;Singh, Minnie;Spector, Benjamin L.;Wende, Helen Vander;Wang, Adrienne M.;Wasko, Brian M.;Olsen, Brady;Kaeberlein, Matt
通讯作者：
Kaeberlein, Matt
影响因子：
9.2
作者：
Coates, PJ;Jamieson, DJ;Hall, PA
通讯作者：
Hall, PA
DOI：
10.1016/j.tem.2009.11.005
发表时间：
2010-03
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Anderson RM;Weindruch R
通讯作者：
Weindruch R
影响因子：
4.5
作者：
Garay E;Campos SE;González de la Cruz J;Gaspar AP;Jinich A;Deluna A
通讯作者：
Deluna A