PXD021939

PXD021939 is an original dataset announced via ProteomeXchange.

Title	LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding
Description	Because 99% of the mitochondrial proteome is encoded by the nucleus, most mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently fold into their functional state. Mitochondrial precursors are imported as unfolded polypeptides due to the limited pore size of the import machinery. For proteins of the mitochondrial matrix and inner membrane, two separate and highly conserved chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding. Here we show that LONP1, a 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 collaborates with mtHSP70 and its co-factors to stabilize a folding intermediate of OXA1L. In the absence of LONP1, the interaction of mtHSP70 with OXA1L is futile and results in substrate-induced coaggregation. Our results identify mitochondrial LONP1 as a critical factor in the mtHSP70 folding pathway and directly demonstrate its long suspected chaperone activity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:35:37.993.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brett Lomenick
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-13 01:59:58	ID requested
1	2020-12-06 23:42:27	announced
⏵ 2	2023-11-14 08:35:38	announced	2023-11-14: Updated project metadata.

Shin CS, Meng S, Garbis SD, Moradian A, Taylor RW, Sweredoski MJ, Lomenick B, Chan DC, LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding. Nat Commun, 12(1):265(2021) [pubmed]

submitter keyword: aggregates, protein homeostasis, mitochondria,human

Spiros D. Garbis
contact affiliation	Proteome Exploration Laboratory Beckman Institute California Institute of Technology
contact email	S.D.Garbis@gmail.com
lab head
Brett Lomenick
contact affiliation	Caltech Proteome Exploration Lab
contact email	lomenick@caltech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021939
     1. Label: PRIDE project
     2. Name: LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding