PXD070578-1

PXD070578 is an original dataset announced via ProteomeXchange.

Title	Mitophagy mitigates mitochondrial dysfunction-triggered activation of mtDNA-cGAS-STING inflammation during autoimmune thyroiditis
Description	Autoimmune thyroiditis (AIT) is a common endocrine disorder characterized by the destruction of thyroid follicles and lymphocytic infiltration, yet its pathogenic mechanisms are not fully understood. This study reveals that chronic oxidative stress during thyroid hormone synthesis in follicular epithelial cells leads to mitochondrial damage and dysfunction. A key finding is the cytosolic leakage of mitochondrial DNA (mtDNA) resulting from this damage, which activates the cGAS-STING innate immune signaling pathway, driving the production of proinflammatory cytokines and exacerbating disease pathogenesis. Conversely, we identify a protective, adaptive mitophagy pathway mediated by the ATM-CHK2 axis. Upon mitochondrial stress, activated CHK2 translocates to mitochondria and phosphorylates the selective autophagy adapter TAX1BP1 at Ser722. This phosphorylation event enhances TAX1BP1's affinity for K63-linked ubiquitin chains on damaged mitochondria, facilitating their clearance via PINK1/Parkin-dependent mitophagy. Impairment of this ATM-CHK2-TAX1BP1 pathway, or genetic ablation of PINK1/Parkin, abrogates mitophagy, leading to amplified mtDNA leakage and hyperactivation of cGAS-STING signaling. Crucially, pharmacological inhibition of STING with C-176 significantly attenuates thyroiditis progression in mouse models.
HostingRepository	iProX
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-10_23:59:56.331.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qiqiang Guo
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-10 23:59:11	ID requested
⏵ 1	2025-11-10 23:59:56	announced

Dataset with its publication pending

submitter keyword: Autoimmune thyroiditis, Mitophagy, Mitochondrial DNA, cGAS-STING signaling, Oxidative stress, Thyroid follicular epithelial cells, TAX1BP1, ATM-CHK2 pathway

Qiqiang Guo
contact affiliation	China Medical University
contact email	qqguo@cmu.edu.cn
lab head
Qiqiang Guo
contact affiliation	China Medical University
contact email	qqguo@cmu.edu.cn
dataset submitter

iProX dataset URI