Mitochondrial localization of St14-encoding transmembrane serine protease is involved in neural stem/progenitor cell bioenergetics through binding to F0F1-ATP synthase complex.
FASEB J
; 33(3): 4327-4340, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30566397
ABSTRACT
Knockdown of the suppression of tumorigenicity 14-encoding type II transmembrane serine protease matriptase (MTP) in neural stem/progenitor (NS/P) cells impairs cell mobility, response to chemo-attractants, and neurovascular niche interaction. In the present study, we showed by Western blot that a portion of MTP can be detected in the mitochondrial fraction of mouse NS/P cells by immunostaining that it is co-stained with the mitochondrial dye MitoTracker (Thermo Fisher Scientific, Waltham, MA, USA) inside the cells. Co-immunoprecipitation showed that MTP is bound to the ß subunit of mitochondrial F0F1-ATP synthase complex (ATP-ß). Cyto-immunofluorescence staining and an in situ proximity ligation assay further confirmed a physical interaction between MTP and ATP-ß. This interaction relied on the presence of both Cls/Clr urchin embryonic growth factor, bone morphogenic protein 1 and low-density lipoprotein receptor motifs of MTP. We found that NS/P cell mitochondrial membrane potential is impaired by MTP knockdown, and ATP synthesis and oxygen consumption rate are significantly reduced in MTP-knockdown NS/P cells. Among the oxidative phosphorylation functions, the greatest effect of MTP knockdown is the reduction by over 50% in the mitochondrial energy reserve capacity. This made MTP-knockdown NS/P cells unable to overcome hydrogen peroxide stress, which leads to cessation of cell growth. This work identifies 2 previously unknown functions for MTP first as a binding protein in the mitochondrial F1F0-ATP synthase complex and second as a regulatory mechanism of mitochondrial bioenergetics. Mitochondrial MTP may serve a protective function for NS/P cells in response to stress.-Fang, J.-D., Tung, H.-H., Lee, S.-L. Mitochondrial localization of St14-encoding transmembrane serine protease is involved in neural stem/progenitor cell bioenergetics through binding to F0F1-ATP synthase complex.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Serina Endopeptidasas
/
ATPasas de Translocación de Protón
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Metabolismo Energético
/
Serina Proteasas
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Células-Madre Neurales
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Proteínas de la Membrana
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Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China