Open AccessCD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells
Author(s) -
Suárez Henar,
Andreu Zoraida,
Mazzeo Carla,
Toribio Víctor,
PérezRivera Aldo Emmanuel,
LópezMartín Soraya,
GarcíaSilva Susana,
Hurtado Begoña,
Morato Esperanza,
Peláez Laura,
Arribas Egoitz Astigarraga,
TolentinoCortez Tarson,
BarredaGómez Gabriel,
Marina Ana Isabel,
Peinado Héctor,
YáñezMó María
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12082
Subject(s) - tetraspanin , mitophagy , microbiology and biotechnology , biology , endosome , secretion , gene knockdown , intracellular , cell , autophagy , cell culture , biochemistry , apoptosis , genetics
Tetraspanins are often used as Extracellular Vesicle (EV) detection markers because of their abundance on these secreted vesicles. However, data on their function on EV biogenesis are controversial and compensatory mechanisms often occur upon gene deletion. To overcome this handicap, we have compared the effects of tetraspanin CD9 gene deletion with those elicited by cytopermeable peptides with blocking properties against tetraspanin CD9. Both CD9 peptide or gene deletion reduced the number of early endosomes. CD9 peptide induced an increase in lysosome numbers, while CD9 deletion augmented the number of MVB and EV secretion, probably because of compensatory CD63 expression upregulation. In vivo , CD9 peptide delayed primary tumour cell growth and reduced metastasis size. These effects on cell proliferation were shown to be concomitant with an impairment in mitochondrial quality control. CD9 KO cells were able to compensate the mitochondrial malfunction by increasing total mitochondrial mass reducing mitophagy. Our data thus provide the first evidence for a functional connection of tetraspanin CD9 with mitophagy in melanoma cells.