2026-10-12T22:36:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33967850 2026-09-22T17:38:10Z category_4 category_7 category_8 category_12 category_13 category_14 category_272 category_46 category_734 category_64 category_128 category_132 portal_5 item_type_3 month_year_09_2026

ppat.1014614.t001 - <p> </p> Smriti Sundar (25091309) Raju S. Rajmani (11134060) Kithiganahalli Narayanaswamy Balaji (9381464) Biochemistry Medicine Microbiology Cell Biology Genetics Molecular Biology Environmental Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer Hematology Infectious Diseases mycobacterium tuberculosis </ confers symmetric dimethylation promotes autophagic degradation process termed ferritinophagy mediated methylation enhances reduced mtb loads promotes ferritinophagy regulating ferritinophagy mediated ferroptosis using loss translational modification replete condition overt accumulation novel post lipid peroxidation infected mice infected cells function studies findings uncover elevated levels deficient mutant cytoplasmic retention critical factor <div><p><i>Mycobacterium tuberculosis</i> (Mtb) increases the availability of free iron, resulting in ferroptosis of macrophages to facilitate its survival and dissemination. A critical factor for elevated levels of labile iron is the overt accumulation of nuclear receptor coactivator 4 (NCOA4), which promotes autophagic degradation of ferritin in a process termed ferritinophagy. Here, we identify a novel post-translational modification on NCOA4 that is essential for its interaction with ferritin in the iron-replete condition of Mtb-infected cells. Specifically, protein arginine methyltransferase 5 (PRMT5) confers symmetric dimethylation on NCOA4, which promotes ferritinophagy-mediated ferroptosis. Using loss-of-function studies, we show that PRMT5 is required for lipid peroxidation, bacterial survival, and dissemination in Mtb-infected mice. Additionally, the overexpression of a methylation-deficient mutant of NCOA4 phenocopies the depletion of PRMT5 and reduces ferritinophagy in Mtb-infected cells. Mechanistically, we identify that PRMT5-mediated methylation enhances the cytoplasmic retention of NCOA4 and reduces its nuclear availability. Thus, our findings uncover the key interaction between NCOA4 and ferritin that regulates ferroptosis and mycobacterial survival during infection. Perturbation of this interaction results in reduced Mtb loads and alleviated disease pathology.</p></div> 2026-09-22T17:55:17Z Dataset Dataset 10.1371/journal.ppat.1014614.t001 https://figshare.com/articles/dataset/ppat_1014614_t001_-_p_p_/33967850 CC BY 4.0