title: Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells.
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.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Chuankai
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Fengli
authors.initials: F
authors.lastname: Guo
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Zulin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmacolgy, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Mickey
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Akshay
authors.initials: A
authors.lastname: Narkar
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Rhonda Trimble
authors.initials: RT
authors.lastname: Ross
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Melainia
authors.initials: M
authors.lastname: McClain
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: rli@stowers.org.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D002455:Cell Division; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D066329:Protein Aggregates; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D013312:Stress, Physiological
chemical_list: D066329:Protein Aggregates