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Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11977-82. doi: 10.1073/pnas.1506054112. Epub 2015 Sep 8.

Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals "aging factors" and mechanism of lifespan asymmetry.

Author information

1
Department of Biochemistry and Biophysics, University of California San Francisco, CA 94143; State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics and Center for Quantitative Biology, Peking University, Beijing 100871, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha 410013, China;
2
Buck Institute for Research on Aging, Novato, CA 94945;
3
Department of Biochemistry and Biophysics, University of California San Francisco, CA 94143;
4
Department of Biochemistry and Biophysics, University of California San Francisco, CA 94143; State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics and Center for Quantitative Biology, Peking University, Beijing 100871, China;
5
State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics and Center for Quantitative Biology, Peking University, Beijing 100871, China;
6
Department of Pathology, University of Washington, Seattle, WA 98195.
7
Buck Institute for Research on Aging, Novato, CA 94945; bkennedy@buckinstitute.org haoli@genome.ucsf.edu.
8
Department of Biochemistry and Biophysics, University of California San Francisco, CA 94143; State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics and Center for Quantitative Biology, Peking University, Beijing 100871, China; bkennedy@buckinstitute.org haoli@genome.ucsf.edu.

Abstract

Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials ("aging factors") through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms.

KEYWORDS:

aging; asymmetric cell division; proteome

PMID:
26351681
PMCID:
PMC4586869
DOI:
10.1073/pnas.1506054112
[Indexed for MEDLINE]
Free PMC Article

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