The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis

Edward M. Germany, Nataliya Zahayko, Mason L. Huebsch, Jennifer L. Fox, Veena Prahlad, Oleh Khalimonchuk

Research output: Contribution to journalArticle

Abstract

Mitochondrial functions are critical for cellular physiology; therefore, several conserved mechanisms are in place to maintain the functional integrity of mitochondria. However, many of the molecular details and components involved in ensuring mitochondrial fidelity remain obscure. Here, we identify a novel role for the conserved mitochondrial AAA ATPase Afg1 in mediating mitochondrial protein homeostasis during aging and in response to various cellular challenges. Saccharomyces cerevisiae cells lacking functional Afg1 are hypersensitive to oxidative insults, unable to tolerate protein misfolding in the matrix compartment and exhibit progressive mitochondrial failure as they age. Loss of the Afg1 ortholog LACE-1 in Caenorhabditis elegans is associated with reduced lifespan, impeded oxidative stress tolerance, impaired mitochondrial proteostasis in the motor neuron circuitry and altered behavioral plasticity. Our results indicate that Afg1 is a novel protein quality control factor, which plays an important evolutionarily conserved role in mitochondrial surveillance, and cellular and organismal health.

Original languageEnglish (US)
Article numberjcs219956
JournalJournal of Cell Science
Volume131
Issue number22
DOIs
StatePublished - Nov 1 2018

Fingerprint

Adenosine Triphosphatases
Mitochondrial Proteins
Caenorhabditis elegans
Health
Motor Neurons
Quality Control
Saccharomyces cerevisiae
Mitochondria
Proteins
Oxidative Stress
Homeostasis

Keywords

  • C. Elegans
  • LACE-1
  • Mitochondria
  • Mitochondrial fidelity
  • Protein homeostasis
  • Yeast

ASJC Scopus subject areas

  • Cell Biology

Cite this

The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis. / Germany, Edward M.; Zahayko, Nataliya; Huebsch, Mason L.; Fox, Jennifer L.; Prahlad, Veena; Khalimonchuk, Oleh.

In: Journal of Cell Science, Vol. 131, No. 22, jcs219956, 01.11.2018.

Research output: Contribution to journalArticle

Germany, Edward M. ; Zahayko, Nataliya ; Huebsch, Mason L. ; Fox, Jennifer L. ; Prahlad, Veena ; Khalimonchuk, Oleh. / The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis. In: Journal of Cell Science. 2018 ; Vol. 131, No. 22.
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