Cr (VI) induced mitophagy via the interaction of HMGA2 and PARK2.
Toxicol Lett
; 333: 261-268, 2020 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-32866567
ABSTRACT
Chromium (Cr) (VI) is a proven toxin, mutagen and carcinogen. Here, the role of high mobility group A2 (HMGA2) mediating Cr (VI)-induced mitophagy was investigated. Cr (VI)-treatment caused the formation of double membrane autophagic vesicles (AVs) engulfing mitochondria and increased the expression of PINK1, PARK2, LC3 as well as HMGA2 particularly in mitochondria in A549 cells. Silencing of HMGA2 by siRNA decreased expression of PINK1, PARK2 and LC3 II especially in mitochondria, while over-expression of HMGA2 increased the expression of them in A549 cells. It indicated that HMGA2 played a critical role in Cr (VI)-induced mitophagy. Most importantly, the results of co-immunoprecipitation showed for the first time that HMGA2 could bind to PARK2 in mitochondria to activate the mitophagy pathway. In BALB/c mice, Cr (VI) increased the expression of PINK1 and PARK2 in lung tissues. Furthermore, over-expression of HMGA2 in BALB/c mice by transfection of plasmid HMGA2 significantly increased the levels of PINK1, PARK2 and LC3 II in lung tissues. Collectively, our data demonstrated that HMGA2 plays an important role in Cr (VI)-induced mitophagy through direct interaction with PARK2 in A549 cells and lung tissue.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromo
/
Proteína HMGA2
/
Ubiquitina-Proteína Ligases
/
Poluentes Ambientais
/
Mitofagia
/
Pulmão
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article