Decorin evokes reversible mitochondrial depolarization in carcinoma and vascular endothelial cells.
Am J Physiol Cell Physiol
; 323(5): C1355-C1373, 2022 11 01.
Article
em En
| MEDLINE
| ID: mdl-36036446
ABSTRACT
Decorin, a small leucine-rich proteoglycan with multiple biological functions, is known to evoke autophagy and mitophagy in both endothelial and cancer cells. Here, we investigated the effects of soluble decorin on mitochondrial homeostasis using live cell imaging and ex vivo angiogenic assays. We discovered that decorin triggers mitochondrial depolarization in triple-negative breast carcinoma, HeLa, and endothelial cells. This bioactivity was mediated by the protein core in a time- and dose-dependent manner and was specific for decorin insofar as biglycan, the closest homolog, failed to trigger depolarization. Mechanistically, we found that the bioactivity of decorin to promote depolarization required the MET receptor and its tyrosine kinase. Moreover, two mitochondrial interacting proteins, mitostatin and mitofusin 2, were essential for downstream decorin effects. Finally, we found that decorin relied on the canonical mitochondrial permeability transition pore to trigger tumor cell mitochondrial depolarization. Collectively, our study implicates decorin as a soluble outside-in regulator of mitochondrial dynamics.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma
/
Células Endoteliais
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Decorina
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article