An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells

Duarte, Alejandra; Castillo, Ana Fernanda; Castilla, Rocı́o; Maloberti, Paula; Paz, Cristina; Podestá, Ernesto J.; Maciel, Fabiana Cornejo

doi:10.1016/j.febslet.2007.07.040

Cited by 28 publications

(28 citation statements)

References 23 publications

(39 reference statements)

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“…Particularly, a tyrosine phosphatase SHP2 (src homology 2-containing phosphotyrosine phosphatase 2) has been indicated as a key protein in regulating steroid synthesis. In this regard, SHP2 participates in the transcriptional regulation of the Acyl-CoA synthetase 4 (ACSL4), which in turn participates in the regulation of intramitochondrial arachidonic acid (AA) levels Duarte et al, 2007;Maloberti et al, 2005). Then, AA lipoxygenated or epoxygenated products induce the expression of the StAR gene (Stocco et al, 2001).…”

Section: Phosphatases In Star Functionmentioning

confidence: 99%

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis

Castillo

Orlando

Helfenberger

et al. 2015

Molecular and Cellular Endocrinology

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Section: Phosphatases In Star Functionmentioning

confidence: 99%

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis

Castillo

Orlando

Helfenberger

et al. 2015

Molecular and Cellular Endocrinology

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“…Its major substrates are palmitoyl-CoA (PCoA) and myristoyl-CoA (MCoA) ( 18 ), which positions Acot2 as a potential regulator of longchain fatty acyl-CoA entry into FAO. While a role for Acot2 has been defi ned in steroidogenic cells ( 19,20 ), its role in highly oxidative tissues is unknown. Here we investigated the biological role of Acot2 in nonsteroidogenic cells.…”

Section: Bioenergetics Analyses In Isolated Mitochondria and Hepatocytesmentioning

confidence: 99%

Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver

Moffat

Bhatia

Nguyen

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org Pathophysiological mechanisms that underlie metabolic dysfunction such as insulin resistance and nonalcoholic fatty liver disease are complex. A role for mitochondrial FA oxidation (FAO) as a driver of dysfunction has been postulated ( 1-3 ), yet the mechanistic link between cellular metabolic dysfunction and mitochondrial FAO remains poorly defi ned ( 2 ). Insight would be gained by a better understanding of FAO. In particular, the modulation of ␤ -oxidation substrates and intermediates by mechanisms within the mitochondria is poorly understood, but is of interest in the context of evidence suggesting that longchain fatty acyl-CoA esters can inhibit FAO ( 4-6 ).Acyl-CoA thioesterases (Acots) in mitochondria, by virtue of their major substrates (long-chain fatty acyl-CoAs) and hydrolase activity which generates FA anion and free CoASH, have the potential to modulate the levels of FAO substrates and intermediates, and consequently to modulate FAO. The Acots are classifi ed as type I or II based on catalytic domain structure, and localize to the cytosol, peroxisomes, and mitochondria. The mitochondrial Acots are Acot2 (mitochondrial matrix) ( 7 ), Acot9 (matrix) ( 8 ), Acot15/Them5 (matrix) ( 9 ), Acot11/Them1 (outside the matrix) ( 10 ), and Acot13/Them2 (outside the matrix) ( 11 ). All are type II thioesterases except for Acot2. The only matrix-localized Acot for which a functional role has been delineated is Acot15. Its germline deletion in mice Abstract Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxidative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad-Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from AdAcot2 mice, phosphorylating O 2 consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effl uxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our fi ndings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix. -Moffat, C., L. Bhatia, T. Nguyen, P. Lynch, M. Wang, D. Wang, O. R. Ilkayeva, X. Han, M. D. Hirschey, S. M. Claypool, and E. L. Seifert. Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in t...

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“…LC n-3 PUFA also have a role in various aspects of reproduction (90) , and are involved in oocyte fertilisation (89) , as well as fetal and infant development (91,92) . Fatty acids and their derivatives are also involved at various stages of folliculogenesis, including during steroidogenesis and the activation of steroid acute regulatory protein (93,94) , as well as during ovulation when luteinising hormone-driven COX-2 expression leads to the production of prostaglandins, essential components in the processes of cumulus oocyte complex expansion and ovulation (95) . The pathology of PCOS is linked with many of the metabolic aberrations for which n-3 PUFA have been shown to exert a positive effect.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Metabolic and hormonal aspects of polycystic ovary syndrome: the impact of diet

2010

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Polycystic ovary syndrome (PCOS) is a common, chronic endocrine condition affecting young women of reproductive age. It is characterised by hyperandrogenaemia, and profound menstrual and ovulatory dysfunction with consequent sub-fertility. A clustering of metabolic aberrations is commonly associated with this condition and these include insulin resistance, disordered lipid metabolism and chronic low-grade inflammation. Overweight and obesity, as well as a degree of adipose tissue dysfunction, are present in a large proportion of women with PCOS, and where present, magnify the inherent hyperandrogenaemia characteristic of the condition, in addition to worsening the metabolic profile. Diet and lifestyle interventions are among the first-line treatments for PCOS, and weight reduction through energy restriction has been shown to exert positive influences on both metabolic and hormonal aspects of this condition. Alterations in carbohydrate amount and type have also been investigated, and more recently, dietary fatty acids, with a particular emphasis on PUFA, have been shown to have a positive impact within this population group. Although it is likely that diet is not the root cause of PCOS, it represents a modifiable variable with the potential to improve the health of women with this condition. Work to date has provided insights into the role of diet in PCOS; however, further work is required to determine the role of nutrients specifically within the context of PCOS, in order to develop more effective, evidence-based dietary guidelines for this condition.

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An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells

Cited by 28 publications

References 23 publications

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis

Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver

Metabolic and hormonal aspects of polycystic ovary syndrome: the impact of diet

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