Lysosomal dysfunction by inactivation of V-ATPase drives innate immune response in C. elegans.
Cell Rep
; 43(5): 114138, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38678555
ABSTRACT
Pathogens target vacuolar ATPase (V-ATPase) to inhibit lysosomal acidification or lysosomal fusion, causing lysosomal dysfunction. However, it remains unknown whether cells can detect dysfunctional lysosomes and initiate an immune response. In this study, we discover that dysfunction of lysosomes caused by inactivation of V-ATPase enhances innate immunity against bacterial infections. We find that lysosomal V-ATPase interacts with DVE-1, whose nuclear localization serves as a proxy for the induction of mitochondrial unfolded protein response (UPRmt). The inactivation of V-ATPase promotes the nuclear localization of DVE-1, activating UPRmt and inducing downstream immune response genes. Furthermore, pathogen resistance conferred by inactivation of V-ATPase requires dve-1 and its downstream immune effectors. Interestingly, animals grow slower after vha RNAi, suggesting that the vha-RNAi-induced immune response costs the most energy through activation of DVE-1, which trades off with growth. This study reveals how dysfunctional lysosomes can trigger an immune response, emphasizing the importance of conserving energy during immune defense.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caenorhabditis elegans
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ATPases Vacuolares Próton-Translocadoras
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Proteínas de Caenorhabditis elegans
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Imunidade Inata
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Lisossomos
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos