LON is the master protease that protects against protein aggregation in human mitochondria through direct degradation of misfolded proteins

Bezawork-Geleta, Ayenachew, Brodie, Erica J., Dougan, David A. and Truscott, Kaye N. (2015) LON is the master protease that protects against protein aggregation in human mitochondria through direct degradation of misfolded proteins. Scientific Reports, 5 . doi:10.1038/srep17397


Author Bezawork-Geleta, Ayenachew
Brodie, Erica J.
Dougan, David A.
Truscott, Kaye N.
Title LON is the master protease that protects against protein aggregation in human mitochondria through direct degradation of misfolded proteins
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1038/srep17397
Open Access Status DOI
Volume 5
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Maintenance of mitochondrial protein homeostasis is critical for proper cellular function. Under normal conditions resident molecular chaperones and proteases maintain protein homeostasis within the organelle. Under conditions of stress however, misfolded proteins accumulate leading to the activation of the mitochondrial unfolded protein response (UPRmt). While molecular chaperone assisted refolding of proteins in mammalian mitochondria has been well documented, the contribution of AAA+ proteases to the maintenance of protein homeostasis in this organelle remains unclear. To address this gap in knowledge we examined the contribution of human mitochondrial matrix proteases, LONM and CLPXP, to the turnover of OTC-∆, a folding incompetent mutant of ornithine transcarbamylase, known to activate UPRmt. Contrary to a model whereby CLPXP is believed to degrade misfolded proteins, we found that LONM, and not CLPXP is responsible for the turnover of OTC-∆ in human mitochondria. To analyse the conformational state of proteins that are recognised by LONM, we examined the turnover of unfolded and aggregated forms of malate dehydrogenase (MDH) and OTC. This analysis revealed that LONM specifically recognises and degrades unfolded, but not aggregated proteins. Since LONM is not upregulated by UPRmt, this pathway may preferentially act to promote chaperone mediated refolding of proteins.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Mon, 12 Jun 2017, 09:58:10 EST by Kirstie Asmussen on behalf of Queensland Brain Institute