Defective mitochondrial ISCs biogenesis switches on IRP1 to fine tune selective mitophagy.
Redox Biol
; 36: 101661, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32795936
ABSTRACT
Both iron metabolism and mitophagy, a selective mitochondrial degradation process via autolysosomal pathway, are fundamental for the cellular well-being. Mitochondria are the major site for iron metabolism, especially the biogenesis of iron-sulfur clusters (ISCs) via the mitochondria-localized ISCs assembly machinery. Here we report that mitochondrial ISCs biogenesis is coupled with receptor-mediated mitophagy in mammalian cells. Perturbation of mitochondrial ISCs biogenesis, either by depleting iron with the iron chelator or by knocking down the core components of the mitochondrial ISCs assembly machinery, triggers FUNDC1-dependent mitophagy. IRP1, one of the cellular iron sensors to maintain iron homeostasis, is crucial for iron stresses induced mitophagy. Knockdown of IRP1 disturbed iron stresses induced mitophagy. Furthermore, IRP1 could bind to a newly characterized IRE in the 5' untranslated region of the Bcl-xL mRNA and suppress its translation. Bcl-xL is an intrinsic inhibitory protein of the mitochondrial phosphatase PGAM5, which catalyzes the dephosphorylation of FUNDC1 for mitophagy activation. Alterations of the IRP1/Bcl-xL axis navigate iron stresses induced mitophagy. We conclude that ISCs serve as physiological signals for mitophagy activation, thus coupling mitophagy with iron metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Mitocondriales
/
Mitofagia
Límite:
Animals
Idioma:
En
Revista:
Redox Biol
Año:
2020
Tipo del documento:
Article