RRC ID 59336
著者 Deng P, Uma Naresh N, Du Y, Lamech LT, Yu J, Zhu LJ, Pukkila-Worley R, Haynes CM.
タイトル Mitochondrial UPR repression during Pseudomonas aeruginosa infection requires the bZIP protein ZIP-3.
ジャーナル Proc Natl Acad Sci U S A
Abstract Mitochondria generate most cellular energy and are targeted by multiple pathogens during infection. In turn, metazoans employ surveillance mechanisms such as the mitochondrial unfolded protein response (UPRmt) to detect and respond to mitochondrial dysfunction as an indicator of infection. The UPRmt is an adaptive transcriptional program regulated by the transcription factor ATFS-1, which induces genes that promote mitochondrial recovery and innate immunity. The bacterial pathogen Pseudomonas aeruginosa produces toxins that disrupt oxidative phosphorylation (OXPHOS), resulting in UPRmt activation. Here, we demonstrate that Pseudomonas aeruginosa exploits an intrinsic negative regulatory mechanism mediated by the Caenorhabditis elegans bZIP protein ZIP-3 to repress UPRmt activation. Strikingly, worms lacking zip-3 were impervious to Pseudomonas aeruginosa-mediated UPRmt repression and resistant to infection. Pathogen-secreted phenazines perturbed mitochondrial function and were the primary cause of UPRmt activation, consistent with these molecules being electron shuttles and virulence determinants. Surprisingly, Pseudomonas aeruginosa unable to produce phenazines and thus elicit UPRmt activation were hypertoxic in zip-3-deletion worms. These data emphasize the significance of virulence-mediated UPRmt repression and the potency of the UPRmt as an antibacterial response.
巻・号 116(13)
ページ 6146-6151
公開日 2019-3-26
DOI 10.1073/pnas.1817259116
PII 1817259116
PMID 30850535
PMC PMC6442607
MeSH Animals Basic-Leucine Zipper Transcription Factors / metabolism* Caenorhabditis elegans / metabolism Caenorhabditis elegans / microbiology* Caenorhabditis elegans Proteins / metabolism* Mitochondria / metabolism* Pseudomonas Infections / metabolism* Pseudomonas Infections / microbiology Pseudomonas aeruginosa Transcription Factors / metabolism* Ubiquitin-Protein Ligases / metabolism Unfolded Protein Response*
IF 9.58
引用数 6
リソース情報
線虫 tm4525 tm4919