Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Loss of vacuolar acidity results in iron sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae

Kenneth L. Chen, Toby N. Ven, Matthew M. Crane, Matthew L.C. Brunner, Adrian K. Pun, Kathleen L. Helget, Katherine Brower, Dexter E. Chen, Ha Doan, Justin D. Dillard-Telm, Ellen Huynh, Yen-Chi Feng, Zili Yan, Alexandra Golubeva, Roy A. Hsu, Raheem Knight, Jessie Levin, Vesal Mobasher, Michael Muir, Victor Omokehinde, Corey Screws, Esin Tunali, Rachael K. Tran, Luz Valdez, Edward Yang, Scott R. Kennedy, Alan J. Herr, Matt Kaeberlein, View ORCID ProfileBrian M. Wasko
doi: https://doi.org/10.1101/2020.01.05.895433
Kenneth L. Chen
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toby N. Ven
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew M. Crane
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew L.C. Brunner
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adrian K. Pun
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen L. Helget
Department of Biology and Biotechnology, University of Houston-Clear Lake, Houston, TX USA 77058
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine Brower
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dexter E. Chen
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ha Doan
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Justin D. Dillard-Telm
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ellen Huynh
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yen-Chi Feng
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zili Yan
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexandra Golubeva
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roy A. Hsu
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raheem Knight
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessie Levin
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vesal Mobasher
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Muir
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Victor Omokehinde
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Corey Screws
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esin Tunali
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rachael K. Tran
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luz Valdez
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edward Yang
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott R. Kennedy
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan J. Herr
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matt Kaeberlein
Department of Pathology, University of Washington, Seattle, WA, USA 98195
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian M. Wasko
Department of Biology and Biotechnology, University of Houston-Clear Lake, Houston, TX USA 77058
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Brian M. Wasko
  • For correspondence: wasko@uhcl.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

The loss of vacuolar/lysosomal acidity is an early event during aging that has been linked to mitochondrial dysfunction. However, it is unclear how loss of vacuolar acidity results in age-related dysfunction. Through unbiased genetic screens, we determined that increased iron uptake can suppress the mitochondrial respiratory deficiency phenotype of yeast vma mutants, which have lost vacuolar acidity due to genetic disruption of the vacuolar ATPase proton pump. Yeast vma mutants exhibited nuclear localization of Aft1, which turns on the iron regulon in response to iron sulfur cluster (ISC) deficiency. This led us to find that loss of vacuolar acidity with age in wildtype yeast causes ISC defects and a DNA damage response. Using microfluidics to investigate aging at the single cell level, we observe grossly divergent trajectories of iron homeostasis within an isogenic and environmentally homogeneous population. One subpopulation of cells fails to mount the expected compensatory iron regulon gene expression program, and suffers progressively severe ISC deficiency with little to no activation of the iron regulon. In contrast, other cells show robust iron regulon activity with limited ISC deficiency, which allows extended passage and survival through a period of genomic instability during aging. These divergent trajectories suggest that iron regulation and ISC homeostasis represent a possible target for aging interventions.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 06, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Loss of vacuolar acidity results in iron sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Loss of vacuolar acidity results in iron sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae
Kenneth L. Chen, Toby N. Ven, Matthew M. Crane, Matthew L.C. Brunner, Adrian K. Pun, Kathleen L. Helget, Katherine Brower, Dexter E. Chen, Ha Doan, Justin D. Dillard-Telm, Ellen Huynh, Yen-Chi Feng, Zili Yan, Alexandra Golubeva, Roy A. Hsu, Raheem Knight, Jessie Levin, Vesal Mobasher, Michael Muir, Victor Omokehinde, Corey Screws, Esin Tunali, Rachael K. Tran, Luz Valdez, Edward Yang, Scott R. Kennedy, Alan J. Herr, Matt Kaeberlein, Brian M. Wasko
bioRxiv 2020.01.05.895433; doi: https://doi.org/10.1101/2020.01.05.895433
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Loss of vacuolar acidity results in iron sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae
Kenneth L. Chen, Toby N. Ven, Matthew M. Crane, Matthew L.C. Brunner, Adrian K. Pun, Kathleen L. Helget, Katherine Brower, Dexter E. Chen, Ha Doan, Justin D. Dillard-Telm, Ellen Huynh, Yen-Chi Feng, Zili Yan, Alexandra Golubeva, Roy A. Hsu, Raheem Knight, Jessie Levin, Vesal Mobasher, Michael Muir, Victor Omokehinde, Corey Screws, Esin Tunali, Rachael K. Tran, Luz Valdez, Edward Yang, Scott R. Kennedy, Alan J. Herr, Matt Kaeberlein, Brian M. Wasko
bioRxiv 2020.01.05.895433; doi: https://doi.org/10.1101/2020.01.05.895433

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Molecular Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1647)
  • Biochemistry (2738)
  • Bioengineering (1907)
  • Bioinformatics (10243)
  • Biophysics (4183)
  • Cancer Biology (3217)
  • Cell Biology (4538)
  • Clinical Trials (135)
  • Developmental Biology (2840)
  • Ecology (4460)
  • Epidemiology (2041)
  • Evolutionary Biology (7231)
  • Genetics (5475)
  • Genomics (6813)
  • Immunology (2388)
  • Microbiology (7480)
  • Molecular Biology (2992)
  • Neuroscience (18584)
  • Paleontology (136)
  • Pathology (472)
  • Pharmacology and Toxicology (780)
  • Physiology (1149)
  • Plant Biology (2706)
  • Scientific Communication and Education (680)
  • Synthetic Biology (888)
  • Systems Biology (2846)
  • Zoology (468)