2026-10-12T04:49:40Z
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2026-09-29T17:32:46Z
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<p>Sph causes mitochondrial fragmentation, cristae disruption, mtDNA release, and cGAS-STING pathway activation.</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
<p><b>(A)</b> Representative transmission electron microscopy images showing mitochondrial ultrastructure in MAC-T cells infected with <i>S. aureus</i> WT, Δ<i>sph</i>, and Δ<i>sph</i>::<i>sph</i> (MOI = 200) for 6 h (n = 3). Original magnification, scale bars, 1 μm. <b>(B)</b> Representative confocal images showing cytosolic mtDNA release in MAC-T cells infected with the indicated <i>S. aureus</i> strains for 6 h (n = 3). Scale bars, 10 μm. <b>(C)</b> Representative transmission electron microscopy images of mitochondrial ultrastructure in MAC-T cells treated with recombinant Sph (32 μg/mL) for 6 h (n = 3). Scale bars, 1 μm. <b>(D)</b> Representative confocal images showing mtDNA release in MAC-T cells treated with recombinant Sph (4 or 32 μg/mL) for 6 h (n = 3). Scale bars, 50 μm. <b>(E)</b> Intracellular ATP levels in MAC-T cells treated with recombinant Sph (4 or 32 μg/mL) for 6 h (n = 6). <b>(F)</b> Relative mRNA expression of the mitochondrial fusion genes <i>Mfn1</i> and <i>Mfn2</i> and the fission-related genes <i>Drp1</i> and <i>Fis1</i> in MAC-T cells following Sph treatment (4 or 32 μg/mL, 6 h) (n = 3). Violin plots illustrate the distribution of mRNA levels across the experimental groups. <b>(G)</b> Expression of POLG protein in MAC-T cells treated with treated with recombinant Sph (32 μg/mL), TMP (2,3,5,6-tetramethylpyrazine; 10 μM), or bortezomib (500 nM) for 6 h (n = 3). <b>(H)</b> Representative immunoblots and quantitative analysis of cGAS-STING pathway proteins in MAC-T cells treated with recombinant Sph (4 or 32 μg/mL) for 6 h (n = 3). Data are presented as mean ± SD. *<i>P</i> < 0.05; **<i>P</i> < 0.01; ns, not significant.</p>
2026-09-29T18:02:15Z
Image
Figure
10.1371/journal.ppat.1014644.g004
https://figshare.com/articles/figure/_p_Sph_causes_mitochondrial_fragmentation_cristae_disruption_mtDNA_release_and_cGAS-STING_pathway_activation_p_/34026597
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