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LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding

Shin, Chun-Shik and Meng, Shuxia and Garbis, Spiros D. and Moradian, Annie and Taylor, Robert W. and Sweredoski, Michael J. and Lomenick, Brett and Chan, David C. (2021) LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding. Nature Communications, 12 . Art. No. 265. ISSN 2041-1723. PMCID PMC7801493. https://resolver.caltech.edu/CaltechAUTHORS:20210111-122716111

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Abstract

Most mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently undergo folding. Mitochondrial precursors are imported as unfolded polypeptides. For proteins of the mitochondrial matrix and inner membrane, two separate chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding. We show that LONP1, an AAA+ protease of the mitochondrial matrix, works with the mtHSP70 chaperone system to promote mitochondrial protein folding. Inhibition of LONP1 results in aggregation of a protein subset similar to that caused by knockdown of DNAJA3, a co-chaperone of mtHSP70. LONP1 is required for DNAJA3 and mtHSP70 solubility, and its ATPase, but not its protease activity, is required for this function. In vitro, LONP1 shows an intrinsic chaperone-like activity and collaborates with mtHSP70 to stabilize a folding intermediate of OXA1L. Our results identify LONP1 as a critical factor in the mtHSP70 folding pathway and demonstrate its proposed chaperone activity.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41467-020-20597-zDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801493PubMed CentralArticle
http://www.ebi.ac.uk/pride/archive/projects/PXD021939Related ItemData
ORCID:
AuthorORCID
Shin, Chun-Shik0000-0002-1382-9876
Garbis, Spiros D.0000-0002-1050-0805
Moradian, Annie0000-0002-0407-2031
Taylor, Robert W.0000-0002-7768-8873
Sweredoski, Michael J.0000-0003-0878-3831
Chan, David C.0000-0002-0191-2154
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 02 April 2020; Accepted 10 December 2020; Published 11 January 2021. Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD021939. Source data are provided with this paper. The authors declare no competing interests. Peer review information: Nature Communications thanks Cheryl F. Lichti, Carolyn Suzuki, and other, anonymous, reviewers for their contributions to hte peer review of this work. Peer review reports are available.
Funders:
Funding AgencyGrant Number
NIHR35 GM127147
Subject Keywords:Chaperones; Mitochondria; Protein translocation
PubMed Central ID:PMC7801493
Record Number:CaltechAUTHORS:20210111-122716111
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210111-122716111
Official Citation:Shin, CS., Meng, S., Garbis, S.D. et al. LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding. Nat Commun 12, 265 (2021). https://doi.org/10.1038/s41467-020-20597-z
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107394
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Jan 2021 20:40
Last Modified:26 Jan 2021 18:20

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