LETM1-Mediated K(+) and Na(+) Homeostasis Regulates Mitochondrial Ca(2+) Efflux.
LETM1-Mediated K(+) and Na(+) Homeostasis Regulates Mitochondrial Ca(2+) Efflux.
复制标题
DOI：
10.3389/fphys.2017.00839
复制
发表时间：
2017
影响因子：
4
通讯作者：
Nowikovsky K
中科院分区：
文献类型：
--
作者：
Austin S;Tavakoli M;Pfeiffer C;Seifert J;Mattarei A;De Stefani D;Zoratti M;Nowikovsky K
Ca2+在线粒体内膜（IMM）上的转运对其生物能量学、细胞死亡和信号传导的功能至关重要。因此，它受到严格监管。最近有人提出letm1 -一种在线粒体K+/H+交换和体积稳态中起关键作用的IMM蛋白-也可以作为Ca2+/H+交换器。本研究首次表明，shRNA降低LETM1基因表达会阻碍线粒体K+/H+和Na+/H+交换。交换活性降低导致基质K+在这些线粒体中积累。此外，LETM1缺失选择性地降低了由NCLX介导的Na+/Ca2+交换，正如在线粒体Ca2+单一转运体（MCU）阻断剂钌红的存在下观察到的那样。这些数据证实了LETM1在单价阳离子稳态中的关键作用，并表明其对线粒体跨膜Ca2+通量的调节可能反映了对Na+/H+交换活性的影响。
Ca2+ transport across the inner membrane of mitochondria (IMM) is of major importance for their functions in bioenergetics, cell death and signaling. It is therefore tightly regulated. It has been recently proposed that LETM1—an IMM protein with a crucial role in mitochondrial K+/H+ exchange and volume homeostasis—also acts as a Ca2+/H+ exchanger. Here we show for the first time that lowering LETM1 gene expression by shRNA hampers mitochondrial K+/H+ and Na+/H+ exchange. Decreased exchange activity resulted in matrix K+ accumulation in these mitochondria. Furthermore, LETM1 depletion selectively decreased Na+/Ca2+ exchange mediated by NCLX, as observed in the presence of ruthenium red, a blocker of the Mitochondrial Ca2+ Uniporter (MCU). These data confirm a key role of LETM1 in monovalent cation homeostasis, and suggest that the effects of its modulation on mitochondrial transmembrane Ca2+ fluxes may reflect those on Na+/H+ exchange activity.
登录
查看更多内容
影响因子：
56.9
作者：
Blomen, Vincent A.;Majek, Peter;Brummelkamp, Thijn R.
通讯作者：
Brummelkamp, Thijn R.
影响因子：
14.8
作者：
Frezza, Christian;Cipolat, Sara;Scorrano, Luca
通讯作者：
Scorrano, Luca
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
64.8
作者：
Baughman, Joshua M.;Perocchi, Fabiana;Girgis, Hany S.;Plovanich, Molly;Belcher-Timme, Casey A.;Sancak, Yasemin;Bao, X. Robert;Strittmatter, Laura;Goldberger, Olga;Bogorad, Roman L.;Koteliansky, Victor;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.
影响因子：
4.8
作者：
Doonan, Patrick J.;Chandramoorthy, Harish C.;Madesh, Muniswamy
通讯作者：
Madesh, Muniswamy