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ATP hydrolysis by yeast Hsp104 determines protein aggregate dissolution and size in vivo.

ABSTRACT: 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.

SUBMITTER: Sathyanarayanan U

PROVIDER: S-EPMC7568574 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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ATP hydrolysis by yeast Hsp104 determines protein aggregate dissolution and size in vivo.

Sathyanarayanan Udhayabhaskar U Musa Marina M Bou Dib Peter P Raimundo Nuno N Milosevic Ira I Krisko Anita A

Nature communications 20201016 1

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 r ...[more]

PMID: 33067463

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