2026-10-09T22:41:01Z
https://api.figshare.com/v2/oai
oai:figshare.com:article/34026573
2026-09-29T17:32:39Z
category_4
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category_272
category_46
category_734
category_106
category_132
category_134
portal_5
item_type_3
month_year_09_2026
<p>Source date.</p>
Yunfei Wei (9412265)
Xinyu Zhao (102214)
Ziyi Yin (4117480)
Yanmin Zhang (391964)
Yaxin Zhai (2562517)
Baihe Zhan (25138380)
Yeling Wang (371383)
Jiakang He (16829817)
Jianfeng Wang (232744)
Xuming Deng (158166)
Lei Xu (78676)
Haihua Feng (198813)
Biochemistry
Microbiology
Cell Biology
Genetics
Molecular Biology
Environmental Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Science Policy
Infectious Diseases
Virology
mitochondrial contact site
dysregulated inflammatory response
disrupt mammary tissues
potential therapeutic target
key virulence determinant
mastitis remain elusive
dependent ferroptosis contribute
>- induced mastitis
>- induced ferroptosis
sting signaling pathway
mediated mtdna release
cgas ), leading
staphylococcus aureus </
promote gpx4 degradation
aureus </
virulence factors
sting axis
potential role
lysosome pathway
underlying mechanisms
thereby eliciting
sphingomyelin phosphodiesterase
organizing system
micos ).
major pathogen
diverse arsenal
cyclic gmp
core component
amp synthase
>; however
<div><p><i>Staphylococcus aureus</i> (<i>S. aureus</i>), a major pathogen of mastitis, employs a diverse arsenal of virulence factors to invade and disrupt mammary tissues, thereby eliciting a complex and dysregulated inflammatory response. Sphingomyelin phosphodiesterase (Sph) has emerged as a key virulence determinant of <i>S. aureus</i>; however, its potential role and underlying mechanisms in mastitis remain elusive. In this study, we demonstrate that Sph deficiency significantly suppresses <i>S. aureus</i>-induced ferroptosis. Mechanistically, Sph disrupts mitochondrial cristae through interaction with Mic60, a core component of the mitochondrial contact site and cristae-organizing system (MICOS). Sph-mediated cytosolic mitochondrial DNA (mtDNA) released is sensed by cyclic GMP-AMP synthase (cGAS), leading to activation of the STING signaling pathway, which further triggers the recruitment of GPX4 into the autophagy-lysosome pathway for degradation. Collectively, our study unveils a novel pathogenic mechanism whereby the <i>S. aureus</i> virulence factor Sph perturbs mitochondrial homeostasis, and engages the cGAS-STING axis to promote GPX4 degradation and ferroptosis, highlighting Sph as a potential therapeutic target for <i>S. aureus</i>-associated mastitis.</p></div>
2026-09-29T18:02:15Z
Dataset
Dataset
10.1371/journal.ppat.1014644.s008
https://figshare.com/articles/dataset/_p_Source_date_p_/34026573
CC BY 4.0