Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells

Chuankai Zhou, Brian D. Slaughter, Jay R. Unruh, Fengli Guo, Zulin Yu, Kristen Mickey, Akshay Narkar, Rhonda Trimble Ross, Melainia McClain, Rong Li

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)530-542
Number of pages13
JournalCell
Volume159
Issue number3
DOIs
StatePublished - Oct 23 2014
Externally publishedYes

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Mitochondria
Organelles
Agglomeration
Proteins
Asymmetric Cell Division
Cell Aggregation
Cells
Association reactions
Mitosis
Ports and harbors
Catalytic Domain
Yeast
Yeasts
Mothers
Aging of materials
Peptides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells. / Zhou, Chuankai; Slaughter, Brian D.; Unruh, Jay R.; Guo, Fengli; Yu, Zulin; Mickey, Kristen; Narkar, Akshay; Ross, Rhonda Trimble; McClain, Melainia; Li, Rong.

In: Cell, Vol. 159, No. 3, 23.10.2014, p. 530-542.

Research output: Contribution to journalArticle

Zhou, C, Slaughter, BD, Unruh, JR, Guo, F, Yu, Z, Mickey, K, Narkar, A, Ross, RT, McClain, M & Li, R 2014, 'Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells', Cell, vol. 159, no. 3, pp. 530-542. https://doi.org/10.1016/j.cell.2014.09.026
Zhou, Chuankai ; Slaughter, Brian D. ; Unruh, Jay R. ; Guo, Fengli ; Yu, Zulin ; Mickey, Kristen ; Narkar, Akshay ; Ross, Rhonda Trimble ; McClain, Melainia ; Li, Rong. / Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells. In: Cell. 2014 ; Vol. 159, No. 3. pp. 530-542.
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