Mitochondrial translocator protein (TSPO): From physiology to cardioprotection

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• 作者：Didier Morin^a ; ^b ; ^{didier.morin@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Julien Musman^a ; ^b ; ^{julien.musman@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Sandrine Pons^a ; ^b ; ^{s.pons@u-pec.fr" class="auth_mail" title="E-mail the corresponding author} ; Alain Berdeaux^a ; ^b ; ^{alain.berdeaux@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Bijan Ghaleh^a ; ^b ; ^{bijan.ghaleh@inserm.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AIF ; apoptosis inducing factor ; ANT ; adenine nucleotide translocase ; Bax ; Bcl-2-associated X protein ; Bcl-2 ; B-cell lymphoma 2 ; IMAC ; inner membrane anion channel ; mPTP ; mitochondrial permeability transition pore ; PBR ; peripheral benzodiazepine receptors ; RIRR ; ROS-induced ROS release ; ROS ; reactive oxygen species ; StAR ; steroidogenic acute regulatory protein ; TSPO ; translocator protein ; VDAC ; voltage-dependent anion channel
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：1 April 2016
• 年：2016
• 卷：105
• 期：Complete
• 页码：1-13
• 全文大小：1192 K

文摘

The mitochondrial translocator protein (TSPO) is a high affinity cholesterol binding protein which is primarily located in the outer mitochondrial membrane where it has been shown to interact with proteins implicated in mitochondrial permeability transition pore (mPTP) formation. TSPO is found in different species and is expressed at high levels in tissues that synthesize steroids but is also present in other peripheral tissues especially in the heart. TSPO has been involved in the import of cholesterol into mitochondria, a key step in steroidogenesis. This constitutes the main established function of the protein which was recently challenged by genetic studies. TSPO has also been associated directly or indirectly with a wide range of cellular functions such as apoptosis, cell proliferation, differentiation, regulation of mitochondrial function or porphyrin transport.

In the heart the role of TSPO remains undefined but a growing body of evidence suggests that TSPO plays a critical role in regulating physiological cardiac function and that TSPO ligands may represent interesting drugs to protect the heart under pathological conditions.

This article briefly reviews current knowledge regarding TSPO and discusses its role in the cardiovascular system under physiological and pathologic conditions. More particularly, it provides evidence that TSPO can represent an alternative strategy to develop new pharmacological agents to protect the myocardium against ischemia–reperfusion injury.