Selective sorting and destruction of mitochondrial membrane proteins in aged yeast

  1. Adam L Hughes  Is a corresponding author
  2. Casey E Hughes
  3. Kiersten A Henderson
  4. Nina Yazvenko
  5. Daniel E Gottschling
  1. Fred Hutchinson Cancer Research Center, United States
  2. University of Utah School of Medicine, United States
  3. Calico Life Sciences, United States

Abstract

Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells. Unlike many common mitochondrial degradation pathways, this system selectively removes a subset of membrane proteins from the mitochondrial inner and outer membranes, while leaving the remainder of the organelle intact. Selective removal of preexisting proteins is achieved by sorting into a mitochondrial-derived compartment, or MDC, followed by release through mitochondrial fission and elimination by autophagy. Formation of MDCs requires the import receptors Tom70/71, and failure to form these structures exacerbates preexisting mitochondrial dysfunction, suggesting that the MDC pathway provides protection to mitochondria in times of stress.

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Author details

  1. Adam L Hughes

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    hughes@biochem.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Casey E Hughes

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kiersten A Henderson

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nina Yazvenko

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel E Gottschling

    Calico Life Sciences, South San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Andrew Dillin, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: December 19, 2015
  2. Accepted: April 18, 2016
  3. Accepted Manuscript published: April 20, 2016 (version 1)
  4. Accepted Manuscript updated: April 25, 2016 (version 2)
  5. Version of Record published: June 1, 2016 (version 3)

Copyright

© 2016, Hughes et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Adam L Hughes
  2. Casey E Hughes
  3. Kiersten A Henderson
  4. Nina Yazvenko
  5. Daniel E Gottschling
(2016)
Selective sorting and destruction of mitochondrial membrane proteins in aged yeast
eLife 5:e13943.
https://doi.org/10.7554/eLife.13943