Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan

Matea Peria, Peter Bou Dib, Sven Dennerlein, Marina Musa, Marina Rudan, Anita Lovric, Andrea Nikolic, Ana Šaric, Sandra Soboeànec, Željka Maeàk, Nuno Raimundo, Anita Kriško

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Article number28751
JournalScientific reports
StatePublished - Jun 27 2016

All Science Journal Classification (ASJC) codes

  • General


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