Organelle plasticity and interactions in cholesterol transport and steroid biosynthesis

Issop, Leeyah; Rone, Malena B.; Papadopoulos, Vassilios

doi:10.1016/j.mce.2012.12.003

Cited by 80 publications

(51 citation statements)

References 125 publications

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“…As a whole therefore, these genes may promote the development of follicles and oocytes but the mechanism is unclear. Previous studies have indicated that pathways involving the DEGs in this study also associate with reproduction except the Notch signaling pathway (Larkin et al, 1996;Lopez-Schier and St Johnston, 2001), TGF-beta signaling pathway (Shi and Massagué, 2003), steroid biosynthesis (Issop et al, 2013), MAPK signaling pathway (Xiao et al, 2007), Wnt signaling pathway (Habas and He, 2006;Ishida-Takagishi et al, 2012) and Jak-STAT signaling pathway (Kisseleva et al, 2002). However, the exact relationship between these signaling networks is not fully understood.…”

Section: Signaling Pathways In Reproductionmentioning

confidence: 67%

Exploring differentially expressed genes in the ovaries of uniparous and multiparous goats using the RNA-Seq (Quantification) method

Ling

Xiang

et al. 2014

Gene

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Section: Signaling Pathways In Reproductionmentioning

confidence: 67%

Exploring differentially expressed genes in the ovaries of uniparous and multiparous goats using the RNA-Seq (Quantification) method

Ling

Xiang

et al. 2014

Gene

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“…STAR is a hormoneinduced protein found at the transduceosome where it likely acts to induce cholesterol transfer from the outer mitochon- drial membrane to the inner mitochondrial membrane (27,40). The goal of these protein/protein interactions and modifications is the creation of a permissive microenvironment that would allow maximal cholesterol delivery to cytochrome P450 11A1, and this steroid production peaks 120 min after hormone or cAMP treatment (28,41). Although both the transduceosome and STAR are rapidly assembled at the outer mitochondrial membrane in response to hormone or cAMP treatment, maximal steroidogenesis occurs within 120 min, indicating a certain delay.…”

Section: Discussionmentioning

confidence: 99%

Protein Modifications Regulate the Role of 14-3-3γ Adaptor Protein in cAMP-induced Steroidogenesis in MA-10 Leydig Cells

Aghazadeh

Blonder

et al. 2014

Journal of Biological Chemistry

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“…voltage-dependent anion channel; the ATPase family, AAA domain-containing 3A; 14-3-3 adaptor proteins; and the steroidogenic acute regulatory protein (STAR) (8). These findings led to biochemical characterization of a hormone-regulated macromolecular protein complex machinery that assists in the intramitochondrial translocation of cholesterol to CYP11A1 (9).…”

mentioning

confidence: 99%

Conditional steroidogenic cell-targeted deletion of TSPO unveils a crucial role in viability and hormone-dependent steroid formation

Fan

Campioli

Midzak

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Translocator protein (TSPO) is a key member of the mitochondrial cholesterol transport complex in steroidogenic tissues. To assess the function of TSPO, we generated two lines of Cre-mediated Tspo conditional knockout (cKO) mice. First, gonadal somatic celltargeting Amhr2-Cre mice were crossed with Tspo-floxed mice to obtain F1 Tspo Amhr2 cKO mice (Tspo fl/fl ;Amhr2-Cre /+). The unexpected Mendelian ratio of 4.4% cKO mice was confirmed by genotyping of 12.5-day-postcoitum (dpc) embryos. As Amhr2-Cre is expressed in gonads at 12.5 dpc, these findings suggest preimplantation selection of embryos. Analysis of expression databases revealed elevated levels of Amhr2 in two-and eight-cell zygotes, suggesting ectopic Tspo silencing before the morula stage and demonstrating elevated embryonic lethality and involvement of TSPO in embryonic development. To circumvent this issue, steroidogenic cell-targeting Nr5a1-Cre mice were crossed with Tspofloxed mice. The resulting Tspo fl/fl ;Nr5a1-Cre /+ mice were born at a normal Mendelian ratio. Nr5a1-driven Tspo cKO mice exhibited highly reduced Tspo levels in adrenal cortex and gonads. Treatment of mice with human chorionic gonadotropin (hCG) resulted in increased circulating testosterone levels despite extensive lipid droplet depletion. In contrast, Nr5a1-driven Tspo cKO mice lost their ability to form corticosterone in response to adrenocorticotropic hormone (ACTH). Important for ACTH-dependent steroidogenesis, Mc2r, Stard1, and Cypa11a1 levels were unaffected, whereas Scarb1 levels were increased and accumulation of lipid droplets was observed, indicative of a blockade of cholesterol utilization for steroidogenesis. TSPO expression in the adrenal medulla and increased epinephrine production were also observed. In conclusion, TSPO was found necessary for preimplantation embryo development and ACTH-stimulated steroid biosynthesis.translocator protein | anti-Mullerian hormone receptor type II | nuclear receptor subfamily 5 group A member 1 | knockout mice | steroidogenesis T he 18-kDa translocator protein (TSPO) is an outer mitochondrial membrane (OMM) protein, originally named the peripheral benzodiazepine receptor (PBR) due to its discovery as a high-affinity binding site for the benzodiazepine diazepam outside of the central nervous system (1). Pharmacological, biochemical, and structural research has revealed TSPO's ability to bind numerous classes of drugs (1-4). Additional investigations also demonstrated that TSPO is a high-affinity cholesterol-binding protein. Cholesterol binding is localized to the C-terminal portion of its fifth transmembrane helix at a conserved cholesterol recognition/association amino acid consensus motif (1, 5). This finding was further supported by recent structural data (6). A search for additional physiological ligands of TSPO revealed that both the tetrapyrole protoporphyrin IX, a heme precursor, and the polypeptide endozepine, a GABA A modulator, bind TSPO, suggesting a role for TSPO in numerous physiological processes (1, 2, 5). Interestingly...

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Organelle plasticity and interactions in cholesterol transport and steroid biosynthesis

Cited by 80 publications

References 125 publications

Exploring differentially expressed genes in the ovaries of uniparous and multiparous goats using the RNA-Seq (Quantification) method

Exploring differentially expressed genes in the ovaries of uniparous and multiparous goats using the RNA-Seq (Quantification) method

Protein Modifications Regulate the Role of 14-3-3γ Adaptor Protein in cAMP-induced Steroidogenesis in MA-10 Leydig Cells

Conditional steroidogenic cell-targeted deletion of TSPO unveils a crucial role in viability and hormone-dependent steroid formation

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