A conserved cysteine‐based redox mechanism sustains TFEB/HLH‐30 activity under persistent stress
Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH‐30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/239614 |
| Acceso en línea: | http://hdl.handle.net/10261/239614 |
| Access Level: | acceso abierto |
| Palabra clave: | Lutathionylation HLH-30 Lysosomes TFE3 TFEB |
| Sumario: | Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH‐30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB/HLH‐30 regulation through a cysteine‐mediated redox switch. Under stress conditions, TFEB‐C212 undergoes oxidation, allowing the formation of intermolecular disulfide bonds that result in TFEB oligomerization. TFEB oligomers display increased resistance to mTORC1‐mediated inactivation and are more stable under prolonged stress conditions. Mutation of the only cysteine residue present in HLH‐30 (C284) significantly reduced its activity, resulting in developmental defects and increased pathogen susceptibility in worms. Therefore, cysteine oxidation represents a new type of TFEB post‐translational modification that functions as a molecular switch to link changes in redox balance with expression of TFEB/HLH‐30 target genes. |
|---|