Journal article
The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis
Journal of cell science, Vol.131(22), p.jcs219956
11/21/2018
DOI: 10.1242/jcs.219956
PMCID: PMC6262775
PMID: 30301782
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.
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
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.
Details
- Title: Subtitle
- The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis
- Creators
- Edward M Germany - Department of Biochemistry, Nebraska Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USANataliya Zahayko - Department of Biochemistry, Nebraska Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USAMason L Huebsch - Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424, USAJennifer L Fox - Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424, USA okhalimonchuk2@unl.edu foxjl@cofc.eduVeena Prahlad - Department of Biology, Aging Mind and Brain Initiative, University of Iowa, Iowa City, IA 52242, USAOleh Khalimonchuk - Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.131(22), p.jcs219956
- Publisher
- England
- DOI
- 10.1242/jcs.219956
- PMID
- 30301782
- PMCID
- PMC6262775
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Grant note
- R01 AG050653 / NIA NIH HHS R01 GM108975 / NIGMS NIH HHS P20 GM103499 / NIGMS NIH HHS T32 GM107001 / NIGMS NIH HHS 52007537 / Howard Hughes Medical Institute P20 RR016461 / NCRR NIH HHS R21 NS097942 / NINDS NIH HHS P30 GM103335 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/21/2018
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983992043602771
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