2012年11月26日 訊 /生物谷BIOON/ --近日，坦普爾大學(xué)醫(yī)學(xué)院和賓夕法尼亞大學(xué)的一個研究小組科學(xué)家們揭示了鈣離子進(jìn)入細(xì)胞線粒體的調(diào)控機(jī)制,。
研究人員一次一個地50個基因的活性，確定了位于線粒體膜內(nèi)側(cè)的蛋白質(zhì)MCUR1是一個加速器,，幫助調(diào)節(jié)鈣進(jìn)入線粒體。結(jié)果刊登在11月25日的Nature Cell Biology雜志上,。
了解如何MCUR1發(fā)揮作用可能有助于治療疾病,，尤其是那些細(xì)胞內(nèi)鈣過量疾病如心血管疾病和中風(fēng)。鈣是調(diào)節(jié)細(xì)胞許多基本生物過程,。過多的鈣在細(xì)胞的線粒體中,，可能會導(dǎo)致心臟功能障礙和神經(jīng)細(xì)胞死亡，保持細(xì)胞中鈣在一個適當(dāng)?shù)乃绞侵陵P(guān)重要的,。
細(xì)胞能量依靠線粒體ATP,，反過來ATP的產(chǎn)生又依賴于進(jìn)入細(xì)胞內(nèi)的鈣。長期以來鈣進(jìn)入線粒體是如何被調(diào)控的細(xì)節(jié)一直為明了,。
為了確定鈣離子進(jìn)入線粒體調(diào)控過程的有關(guān)基因,。研究人員開發(fā)出一種有針對性的RNA干擾（RNAi）技術(shù)，篩選50個線粒體蛋白質(zhì),，測試是否消除這些基因功能,，每一個單獨(dú)的鈣進(jìn)入線粒體會改變運(yùn)動。
他們發(fā)現(xiàn)了一種線粒體內(nèi)膜蛋白質(zhì)MCUR1調(diào)節(jié)鈣離子通道,。MCUR1是一種鈣通道孔單向轉(zhuǎn)運(yùn)體,。當(dāng)MCUR1附著于鈣通道孔時，它是具有功能性的,，但當(dāng)它未附著時,，它是不活躍的,。MCUR1活動水平增加導(dǎo)致線粒體鈣水平額外的提高。
控制鈣進(jìn)入線粒體作為一個有針對性的治療方式,，可以治療一些疾病如缺血再灌注損傷,，中風(fēng)，腦損傷,，缺血和心肌梗死等。我們要控制鈣進(jìn)入線粒體,，還需進(jìn)一步研究其中確切的分子機(jī)制,。（生物谷：Bioon.com）
doi:10.1038/ncb2622
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MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism
Karthik Mallilankaraman,César Cárdenas,Patrick J. Doonan,et al.
Ca2+ flux across the mitochondrial inner membrane regulates bioenergetics, cytoplasmic Ca2+ signals and activation of cell death pathways. Mitochondrial Ca2+ uptake occurs at regions of close apposition with intracellular Ca2+ release, driven by the inner membrane voltage generated by oxidative phosphorylation and mediated by a Ca2+ selective ion channel (MiCa; ref. 15) called the uniporter whose complete molecular identity remains unknown. Mitochondrial calcium uniporter (MCU) was recently identified as the likely ion-conducting pore19, 20. In addition, MICU1 was identified as a mitochondrial regulator of uniporter-mediated Ca2+ uptake in HeLa cells21, 22. Here we identified CCDC90A, hereafter referred to as MCUR1 (mitochondrial calcium uniporter regulator 1), an integral membrane protein required for MCU-dependent mitochondrial Ca2+ uptake. MCUR1 binds to MCU and regulates ruthenium-red-sensitive MCU-dependent Ca2+ uptake. MCUR1 knockdown does not alter MCU localization, but abrogates Ca2+ uptake by energized mitochondria in intact and permeabilized cells. Ablation of MCUR1 disrupts oxidative phosphorylation, lowers cellular ATP and activates AMP kinase-dependent pro-survival autophagy. Thus, MCUR1 is a critical component of a mitochondrial uniporter channel complex required for mitochondrial Ca2+ uptake and maintenance of normal cellular bioenergetics.
