Lack of adrenal TSPO/PBR expression in hamsters reinforces correlation to triglyceride metabolism.
Lack of adrenal TSPO/PBR expression in hamsters reinforces correlation to triglyceride metabolism.
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DOI：
10.1530/joe-20-0189
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Selvaraj V
中科院分区：
文献类型：
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作者：
Koganti PP;Selvaraj V
尽管线粒体转位蛋白(TSPO)是一种高度保守的蛋白质，但它的确切作用仍然不清楚。TSPO以前被称为外周苯二氮卓受体(PBR)。研究推翻了将TSPO/PBR描述为类固醇生成线粒体胆固醇转运体的假设模型，填补了这一空白，证据表明，TSPO/PBR可以影响不同模型系统的线粒体代谢功能。我们先前报道，TSPO/PBR缺陷的类固醇生成细胞上调线粒体脂肪酸氧化，并且TSPO/PBR的表达与活跃于甘油三酯代谢或脂肪储存的组织呈显著正相关。尽管如此，强调先前工作中的不一致之处已引起报复，有可能扼杀进展。一个经常被认为支持胆固醇输入功能的事实是，没有高表达TSPO/PBR的类固醇合成细胞类型。在这项研究中，我们研究了仓鼠肾上腺，它在皮质中没有脂滴，很大程度上依赖于类固醇的生物合成和摄取。我们发现，与小鼠相比，TSPO在仓鼠肾上腺中的表达是不可察觉的。这一观察结果与CPT1A在仓鼠肾上腺中的低表达是一致的，这表明与小鼠相比，线粒体脂肪酸氧化能力最低。这些发现进一步证实，TSPO/PBR功能的广受欢迎的机制仍然与细胞甘油三酯代谢的程度有关。因此，TSPO/PBR可能具有仅与类固醇合成系统有关的稳态功能，该系统管理与脂滴相关的甘油三酯。
Despite being a highly conserved protein, the precise role of the mitochondrial translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), remains elusive. Void created by studies that overturned a presumptive model that described TSPO/PBR as a mitochondrial cholesterol transporter for steroidogenesis, has been filled with evidence that it can affect mitochondrial metabolic functions across different model systems. We previously reported that TSPO/PBR deficient steroidogenic cells upregulate mitochondrial fatty acid oxidation, and presented a strong positive correlation between TSPO/PBR expression and tissues active in triglyceride metabolism or lipid storage. Nevertheless, the highlighting of inconsistencies in prior work has provoked reprisals that threaten to stifle progress. One frequent factoid presented as being supportive of a cholesterol import function is that there are no steroid-synthesizing cell types without high TSPO/PBR expression. In this study, we examine the hamster adrenal gland that is devoid of lipid droplets in the cortex and largely relies on de novo cholesterol biosynthesis and uptake for steroidogenesis. We find that Tspo expression in the hamster adrenal is imperceptible compared to the mouse. This observation is consistent with a substantially low expression of Cpt1a in the hamster adrenal, indicating minimal mitochondrial fatty acid oxidation capacity compared to the mouse. These findings provide further reinforcement that the much sought-after mechanism of TSPO/PBR function remains correlated with the extent of cellular triglyceride metabolism. Thus, TSPO/PBR could have a homeostatic function relevant only to steroidogenic systems that manage triglycerides associated with lipid droplets.