Organelle-Based Aggregation and Retention of Damaged Proteins in Asymmetrically Dividing Cells
| Autor: | Fengli Guo, Kristen Mickey, Rong Li, Jay R. Unruh, Chuankai Zhou, Zulin Yu, Brian D. Slaughter, Melainia McClain, Akshay Narkar, Rhonda Trimble Ross |
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| Rok vydání: | 2014 |
| Předmět: |
Cell division
Biochemistry Genetics and Molecular Biology(all) Saccharomyces cerevisiae Mitochondrion Protein aggregation Biology Endoplasmic Reticulum Article General Biochemistry Genetics and Molecular Biology Mitochondria Cell biology Protein Aggregates Cytosol Stress Physiological Protein Biosynthesis Organelle Asymmetric cell division Protein biosynthesis Mitosis Cell Division |
| Zdroj: | Cell. 159:530-542 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.09.026 |
| Popis: | SummaryAggregation of damaged or misfolded proteins is a protective mechanism against proteotoxic stress, abnormalities of which underlie many aging-related diseases. Here, we show that in asymmetrically dividing yeast cells, aggregation of cytosolic misfolded proteins does not occur spontaneously but requires new polypeptide synthesis and is restricted to the surface of ER, which harbors the majority of active translation sites. Protein aggregates formed on ER are frequently also associated with or are later captured by mitochondria, greatly constraining aggregate mobility. During mitosis, aggregates are tethered to well-anchored maternal mitochondria, whereas mitochondria acquired by the bud are largely free of aggregates. Disruption of aggregate-mitochondria association resulted in increased mobility and leakage of mother-accumulated aggregates into the bud. Cells with advanced replicative age exhibit gradual decline of aggregates-mitochondria association, likely contributing to their diminished ability to rejuvenate through asymmetric cell division. |
| Databáze: | OpenAIRE |
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