TY - JOUR
T1 - Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells
AU - Zhou, Chuankai
AU - Slaughter, Brian D.
AU - Unruh, Jay R.
AU - Guo, Fengli
AU - Yu, Zulin
AU - Mickey, Kristen
AU - Narkar, Akshay
AU - Ross, Rhonda Trimble
AU - McClain, Melainia
AU - Li, Rong
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/10/23
Y1 - 2014/10/23
N2 - Aggregation 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.
AB - Aggregation 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84908269537&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.09.026
DO - 10.1016/j.cell.2014.09.026
M3 - Article
C2 - 25417105
AN - SCOPUS:84908269537
SN - 0092-8674
VL - 159
SP - 530
EP - 542
JO - Cell
JF - Cell
IS - 3
ER -