调节器
生物
线粒体
细胞生物学
蛋白质稳态
脂质体
转录因子
酿酒酵母
遗传学
生物化学
脂类学
酵母
基因
作者
Vladimir I. Titorenko,Anna Leonov,Anthony Arlia‐Ciommo,Younes Medkour,Veronika Svistkova
标识
DOI:10.1096/fasebj.30.1_supplement.1100.2
摘要
Exogenously added lithocholic bile acid (LCA) is known to extend the chronological lifespan of the yeast Saccharomyces cerevisiae , accumulate in mitochondria and alter mitochondrial membrane lipidome. Using quantitative mass spectrometry, we demonstrated that LCA alters the age‐related dynamics of changes in levels of many mitochondrial proteins, as well as numerous proteins in cellular locations outside of mitochondria. These proteins belong to two regulons, each modulated by a different mitochondrial dysfunction; we call them a partial mitochondrial dysfunction regulon and an oxidative stress regulon. Proteins constituting these regulons (1) can be divided into several “clusters”, each of which denotes a distinct type of partial mitochondrial dysfunction that elicits a different signaling pathway mediated by a discrete set of transcription factors; (2) exhibit three different patterns of the age‐related dynamics of changes in their cellular levels; and (3) are encoded by genes whose expression is regulated by the transcription factors Rtg1p/Rtg2p/Rtg3p, Sfp1p, Aft1p, Yap1p, Msn2p/Msn4p, Skn7p and Hog1p, each of which is essential for longevity extension by LCA. Our findings suggest that LCA‐driven changes in mitochondrial lipidome alter mitochondrial proteome and functionality, thereby enabling mitochondria to operate as signaling organelles that orchestrate an establishment of an anti‐aging transcriptional program for many longevity‐defining nuclear genes. We propose a model for how such LCA‐driven changes early and late in life of chronologically aging yeast cause a stepwise development of an anti‐aging cellular pattern and its maintenance throughout lifespan. Support or Funding Information Supported by NSERC of Canada.
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