Optineurin E50K triggers BDNF deficiency-mediated mitochondrial dysfunction in retinal photoreceptor cell line.
Biochem Biophys Res Commun
; 503(4): 2690-2697, 2018 09 18.
Article
em En
| MEDLINE
| ID: mdl-30100066
ABSTRACT
Optineurin (OPTN) mutations are linked to glaucoma pathology and E50K mutation shows massive cell death in photoreceptor cells and retinal ganglion cells. However, little is known about E50K-mediated mitochondrial dysfunction in photoreceptor cell degeneration. We here show that overexpression of E50K expression triggered BDNF deficiency, leading to Bax activation in RGC-5â¯cells. BDNF deficiency induced mitochondrial dysfunction by decreasing mitochondrial maximal respiration and reducing intracellular ATP level in RGC-5â¯cells. However, BDNF deficiency did not alter mitochondrial dynamics. Also, BDNF deficiency resulted in LC3-mediated mitophagosome formation in RGC-5â¯cells. These results strongly suggest that E50K-mediated BDNF deficiency plays a critical role in compromised mitochondrial function in glaucomatous photoreceptor cell degeneration.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Neurotrófico Derivado do Encéfalo
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Células Fotorreceptoras de Vertebrados
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Fator de Transcrição TFIIIA
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Proteína X Associada a bcl-2
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Proteínas Associadas aos Microtúbulos
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article