Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation: A novel gain-of-function mechanism

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Castro, JP (Autor) Outra; Fernando, R (Autor) Outra; Reeg, S (Autor) Outra; Meinl, W (Autor) Outra; Almeida, Henrique (Autor) FMUP; Grune, T (Autor) Outra

Revista

Título: Redox Biology

Vol. 21

ISSN: 2213-2317

Editora: Elsevier

Indexação

ISI Web of Knowledge - 9 Citações

Outras Informações

ID Authenticus: P-00Q-EN0

DOI: 10.1016/j.redox.2019.101108

Abstract (EN): Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10