PXD062741-1

PXD062741 is an original dataset announced via ProteomeXchange.

Title	Sub-cellular in vivo cardiac proteomics of sarcomere and ribosome interactomes identifies skeletal NACA's role in mitochondrial protein sorting.
Description	Background: Proteostasis and the regulation of protein folding and sorting play a critical role in maintaining cellular homeostasis. The failure of proteostasis contributes to heart failure and aging, but, despite its importance, the mechanisms and factors regulating proteostasis in cardiomyocytes remain poorly characterized. Methods: Subcellular proteomes of cardiomyocytes were analyzed in vivo using biotin proximity labeling in mouse hearts. We employed a novel homology-independent targeting integration strategy for genetic tagging and for substitution of the muscle-specific skNAC isoform with the ubiquitous short isoform in cardiomyocytes. Results: We identified hundreds of proteins localized to the Z- and M-lines of sarcomeres, the ribosomes, and the desmosomes, including multiple chaperones. A universal homology-independent targeted integration strategy allowed us to genetically tag endogenous genes in the mouse heart and confirm protein localization. We identified the large muscle-specific isoform of the nascent polypeptide-associated complex protein skNAC as Z-line and ribosome associated protein. Replacement of skNAC with a ubiquitous isoform induced dilated cardiomyopathy, accompanied by altered ribosome positioning, reduced mitochondrial protein levels, and increased endoplasmic reticulum proteins. Conclusions: We unraveled the cardiomyocyte subcellular proteome and show that skNAC, an isoform down-regulated in disease, is a key ribosome and Z-line associated protein specifically responsible for the sorting of cardiomyocytes mitochondrial versus ER proteins.
HostingRepository	PRIDE
AnnounceDate	2025-12-03
AnnouncementXML	Submission_2025-12-02_16:38:42.815.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	biotinylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-08 09:18:47	ID requested
⏵ 1	2025-12-02 16:38:43	announced

Dataset with its publication pending

submitter keyword: cardiomyocyte, proximity labeling, skNAC

Izhak Kehat
contact affiliation	Dept. of Physiology, biophysics, and systems biology The Ruth and Bruce Rappaport Faculty of Medicine Technion- Israel Institute of Technology
contact email	ikehat@technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062741
     1. Label: PRIDE project
     2. Name: Sub-cellular in vivo cardiac proteomics of sarcomere and ribosome interactomes identifies skeletal NACA's role in mitochondrial protein sorting.