title: Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan.
abstract: In cells living under optimal conditions, protein folding defects are usually prevented by the action of chaperones. Here, we investigate the cell-wide consequences of loss of chaperone function in cytosol, mitochondria or the endoplasmic reticulum (ER) in budding yeast. We find that the decline in chaperone activity in each compartment results in loss of respiration, demonstrating the dependence of mitochondrial activity on cell-wide proteostasis. Furthermore, each chaperone deficiency triggers a response, presumably via the communication among the folding environments of distinct cellular compartments, termed here the cross-organelle stress response (CORE). The proposed CORE pathway encompasses activation of protein conformational maintenance machineries, antioxidant enzymes, and metabolic changes simultaneously in the cytosol, mitochondria, and the ER. CORE induction extends replicative and chronological lifespan in budding yeast, highlighting its protective role against moderate proteotoxicity and its consequences such as the decline in respiration. Our findings accentuate that organelles do not function in isolation, but are integrated in a functional crosstalk, while also highlighting the importance of organelle communication in aging and age-related diseases.
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Matea
authors.initials: M
authors.lastname: Perić
authors.affiliation: Universitätsmedizin Göttingen, Institut für Zellbiochemie, Humboldtallee 23, D-37073 Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bou Dib
authors.affiliation: Universitätsmedizin Göttingen, Institut für Zellbiochemie, Humboldtallee 23, D-37073 Göttingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Dennerlein
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Musa
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Rudan
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Lovrić
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nikolić
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Šarić
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sobočanec
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
authors.forename: Željka
authors.initials: Ž
authors.lastname: Mačak
authors.affiliation: Universitätsmedizin Göttingen, Institut für Zellbiochemie, Humboldtallee 23, D-37073 Göttingen, Germany.
authors.forename: Nuno
authors.initials: N
authors.lastname: Raimundo
authors.affiliation: Mediterranean Institute for Life Sciences - MedILS, Meštrovićevo šetalište 45, 21000 Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Kriško
mesh_terms: D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins