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Structural basis and regulation of the reductive stress response.
Manford, Andrew G; Mena, Elijah L; Shih, Karen Y; Gee, Christine L; McMinimy, Rachael; Martínez-González, Brenda; Sherriff, Rumi; Lew, Brandon; Zoltek, Madeline; Rodríguez-Pérez, Fernando; Woldesenbet, Makda; Kuriyan, John; Rape, Michael.
Afiliação
  • Manford AG; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Mena EL; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Shih KY; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Gee CL; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
  • McMinimy R; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Martínez-González B; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Sherriff R; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Lew B; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Zoltek M; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Rodríguez-Pérez F; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Woldesenbet M; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
  • Kuriyan J; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berk
  • Rape M; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berk
Cell ; 184(21): 5375-5390.e16, 2021 10 14.
Article em En | MEDLINE | ID: mdl-34562363
ABSTRACT
Although oxidative phosphorylation is best known for producing ATP, it also yields reactive oxygen species (ROS) as invariant byproducts. Depletion of ROS below their physiological levels, a phenomenon known as reductive stress, impedes cellular signaling and has been linked to cancer, diabetes, and cardiomyopathy. Cells alleviate reductive stress by ubiquitylating and degrading the mitochondrial gatekeeper FNIP1, yet it is unknown how the responsible E3 ligase CUL2FEM1B can bind its target based on redox state and how this is adjusted to changing cellular environments. Here, we show that CUL2FEM1B relies on zinc as a molecular glue to selectively recruit reduced FNIP1 during reductive stress. FNIP1 ubiquitylation is gated by pseudosubstrate inhibitors of the BEX family, which prevent premature FNIP1 degradation to protect cells from unwarranted ROS accumulation. FEM1B gain-of-function mutation and BEX deletion elicit similar developmental syndromes, showing that the zinc-dependent reductive stress response must be tightly regulated to maintain cellular and organismal homeostasis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse Fisiológico Limite: Animals / Female / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse Fisiológico Limite: Animals / Female / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article