Mitochondria-associated membrane formation in hormone-stimulated Leydig cell steroidogenesis: role of ATAD3.
Endocrinology
; 156(1): 334-45, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25375035
ABSTRACT
Leydig cell steroidogenesis is a multistep process that takes place in the mitochondria and endoplasmic reticulum (ER). The physical association between these 2 organelles could facilitate both steroidogenesis substrate availability and mitochondrial product passage to steroidogenic enzymes in the ER, thus regulating the rate of steroid formation. Confocal microscopy, using antisera against organelle-specific antigens, and electron microscopy studies demonstrated that there is an increase in the number of mitochondria-ER contact sites in response to hormone treatment in MA-10 mouse tumor Leydig cells. Electron tomography and 3-dimensional reconstruction allowed for the visualization of mitochondria-associated membranes (MAMs). MAMs were isolated and found to contain the 67-kDa long isoform of the adenosine triphosphatase (ATPase) family, AAA domain-containing protein 3 (ATAD3). The 67-kDa ATAD3 is anchored in the inner mitochondrial membrane and is enriched in outer-inner mitochondrial membrane contact sites. ATAD3-depleted MA-10 cells showed reduced production of steroids in response to human choriogonadotropin but not to 22R-hydroxycholesterol treatment, indicating a role of ATAD3 in the delivery of the substrate cholesterol into the mitochondria. The N terminus of ATAD3 contains 50 amino acids that have been proposed to insert into the outer mitochondrial membrane and associated organelles such as the ER. Deletion of the ATAD3 N terminus resulted in the reduction of hormone-stimulated progesterone biosynthesis, suggesting a role of ATAD3 in mitochondria-ER contact site formation. Taken together, these results demonstrate that the hormone-induced, ATAD3-mediated, MAM formation participates in the optimal transfer of cholesterol from the ER into mitochondria for steroidogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Córtex Suprarrenal
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Adenosina Trifosfatases
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Proteínas Mitocondriais
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Membranas Mitocondriais
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Células Intersticiais do Testículo
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article