TY - JOUR TI - Glucose intake hampers PKA-regulated HSP90 chaperone activity AU - Chen, Yu-Chen AU - Jiang, Pei-Heng AU - Chen, Hsuan-Ming AU - Chen, Chang-Han AU - Wang, Yi-Ting AU - Chen, Yu-Ju AU - Yu, Chia-Jung AU - Teng, Shu-Chun A2 - Dillin, Andrew A2 - Cole, Philip A VL - 7 PY - 2018 DA - 2018/12/05 SP - e39925 C1 - eLife 2018;7:e39925 DO - 10.7554/eLife.39925 UR - https://doi.org/10.7554/eLife.39925 AB - Aging is an intricate phenomenon associated with the gradual loss of physiological functions, and both nutrient sensing and proteostasis control lifespan. Although multiple approaches have facilitated the identification of candidate genes that govern longevity, the molecular mechanisms that link aging pathways are still elusive. Here, we conducted a quantitative mass spectrometry screen and identified all phosphorylation/dephosphorylation sites on yeast proteins that significantly responded to calorie restriction, a well-established approach to extend lifespan. Functional screening of 135 potential regulators uncovered that Ids2 is activated by PP2C under CR and inactivated by PKA under glucose intake. ids2Δ or ids2 phosphomimetic cells displayed heat sensitivity and lifespan shortening. Ids2 serves as a co-chaperone to form a complex with Hsc82 or the redundant Hsp82, and phosphorylation impedes its association with chaperone HSP90. Thus, PP2C and PKA may orchestrate glucose sensing and protein folding to enable cells to maintain protein quality for sustained longevity. KW - chaperone KW - calorie restriction KW - phosphorylation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -