TY - JOUR
T1 - ATP hydrolysis by yeast Hsp104 determines protein aggregate dissolution and size in vivo
AU - Sathyanarayanan, Udhayabhaskar
AU - Musa, Marina
AU - Bou Dib, Peter
AU - Raimundo, Nuno
AU - Milosevic, Ira
AU - Krisko, Anita
N1 - Funding Information:
A.K. is supported by the Heisenberg grant from the Deutsche Forschungsgemeinschaft. M.M. was supported by the Mediterranean Institute for Life Sciences, as well as by FEBS and EMBO short-term fellowships; grant 337327 from the European Research Council to N.R.; I.M. is supported by an Emmy Noether Award from the Deutsche For-schungsgemeinschaft. The authors are grateful to Mr. Dirk Schwitters for technical assistance. The authors would like to thank Prof. Yves Barral for sharing the yeast strains; to Dr. Patricia Kane, Dr. Krszysztof Liberek, and Dr. Antonios Makris for sharing plasmids. A.K. is grateful to Prof. Tiago Outeiro, Dr. Diana Lazaro, Prof. Miroslav Radman, and Prof. Yves Barral for valuable discussions. The authors are grateful to anonymous Reviewers for evaluating this work and for their help in making it better.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Signs of proteostasis failure often entwine with those of metabolic stress at the cellular level. Here, we study protein sequestration during glucose deprivation-induced ATP decline in Saccharomyces cerevisiae. Using live-cell imaging, we find that sequestration of misfolded proteins and nascent polypeptides into two distinct compartments, stress granules, and Q-bodies, is triggered by the exhaustion of ATP. Both compartments readily dissolve in a PKA-dependent manner within minutes of glucose reintroduction and ATP level restoration. We identify the ATP hydrolase activity of Hsp104 disaggregase as the critical ATP-consuming process determining compartments abundance and size, even in optimal conditions. Sequestration of proteins into distinct compartments during acute metabolic stress and their retrieval during the recovery phase provide a competitive fitness advantage, likely promoting cell survival during stress.
AB - Signs of proteostasis failure often entwine with those of metabolic stress at the cellular level. Here, we study protein sequestration during glucose deprivation-induced ATP decline in Saccharomyces cerevisiae. Using live-cell imaging, we find that sequestration of misfolded proteins and nascent polypeptides into two distinct compartments, stress granules, and Q-bodies, is triggered by the exhaustion of ATP. Both compartments readily dissolve in a PKA-dependent manner within minutes of glucose reintroduction and ATP level restoration. We identify the ATP hydrolase activity of Hsp104 disaggregase as the critical ATP-consuming process determining compartments abundance and size, even in optimal conditions. Sequestration of proteins into distinct compartments during acute metabolic stress and their retrieval during the recovery phase provide a competitive fitness advantage, likely promoting cell survival during stress.
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U2 - 10.1038/s41467-020-19104-1
DO - 10.1038/s41467-020-19104-1
M3 - Article
C2 - 33067463
AN - SCOPUS:85092635698
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5226
ER -