Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria.
Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria.
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DOI：
10.1007/s10863-013-9500-5
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发表时间：
2013-06
影响因子：
3
通讯作者：
Stowe, David F.
中科院分区：
文献类型：
--
作者：
Boelens, Age D.;Pradhan, Ranjan K.;Blomeyer, Christoph A.;Camara, Amadou K. S.;Dash, Ranjan K.;Stowe, David F.
关键词：
心脏线粒体基质(m)游离Ca2+ ([Ca2+]m)主要通过Ca2+单转运体（CU）的Ca2+摄取而增加。通过CU的Ca2+摄取被外基质(e) Mg2+ ([Mg2+]e)衰减。[Ca2+]m如何通过[Ca2+]e和[Mg2+]e的生理水平相互作用动态调节，以及这种相互作用如何改变生物能量学尚不清楚。我们假设，当[Mg2+]e通过CU调节Ca2+摄取时，它也以基质Ca2+诱导和基质Ca2+独立的方式改变生物能量学。为了验证这一点，我们测量了豚鼠心脏线粒体中[Ca2+]e， [Ca2+]m， [Mg2+]e和[Mg2+]m的荧光光谱变化，以响应添加的CaCl2 （0-0.6 mM； 1 mM EGTA缓冲液）和/不添加的MgCl2 （0-2 mM）。同时，我们评估了添加CaCl2和MgCl2对NADH、膜电位（ΔΨm）和呼吸的影响。我们发现≥0.125 mM MgCl2显著减弱cu介导的Ca2+摄取和[Ca2+]m。增量[Mg2+]e并没有降低初始Ca2+摄取，但减弱了随后较慢的Ca2+摄取，因此[Ca2+]m随时间保持不变。添加CaCl2而不添加MgCl2，使[Ca2+]m从46 nM增加到221 nM，使状态3 NADH氧化和呼吸增加15%；高达868 nM [Ca2+]m并没有增加NADH氧化或呼吸作用。添加MgCl2没有增加[Mg2+]m，但通过其直接作用降低Ca2+的摄取改变了生物能量学。然而，在给定的[Ca2+]m下，状态3呼吸逐渐减弱，状态4呼吸因较高的[Mg2+]e而增强。因此，在不改变[Mg2+]m的情况下，[Mg2+]e可以独立于cu介导的Ca2+运输调节生物能量。
Cardiac mitochondrial matrix (m) free Ca2+ ([Ca2+]m) increases primarily by Ca2+ uptake through the Ca2+ uniporter (CU). Ca2+ uptake via the CU is attenuated by extra-matrix (e) Mg2+ ([Mg2+]e). How [Ca2+]m is dynamically modulated by interacting physiological levels of [Ca2+]e and [Mg2+]e and how this interaction alters bioenergetics is not well understood. We postulated that as [Mg2+]e modulates Ca2+ uptake via the CU, it also alters bioenergetics in a matrix Ca2+–induced and matrix Ca2+–independent manner. To test this, we measured changes in [Ca2+]e, [Ca2+]m, [Mg2+]e and [Mg2+]m spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl2 (0–0.6 mM; 1 mM EGTA buffer) with/without added MgCl2 (0–2 mM). In parallel, we assessed effects of added CaCl2 and MgCl2 on NADH, membrane potential (ΔΨm), and respiration. We found that ≥0.125 mM MgCl2 significantly attenuated CU-mediated Ca2+ uptake and [Ca2+]m. Incremental [Mg2+]e did not reduce initial Ca2+uptake but attenuated the subsequent slower Ca2+ uptake, so that [Ca2+]m remained unaltered over time. Adding CaCl2 without MgCl2 to attain a [Ca2+]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15%; up to 868 nM [Ca2+]m did not additionally enhance NADH oxidation or respiration. Adding MgCl2 did not increase [Mg2+]m but it altered bioenergetics by its direct effect to decrease Ca2+ uptake. However, at a given [Ca2+]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg2+]e. Thus, [Mg2+]e without a change in [Mg2+]m can modulate bioenergetics independently of CU-mediated Ca2+ transport.
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影响因子：
5.5
作者：
Camara, Amadou K. S.;Aldakkak, Mohammed;Stowe, David F.
通讯作者：
Stowe, David F.
影响因子：
3.5
作者：
BRAGADIN, M;POZZAN, T;AZZONE, GF
通讯作者：
AZZONE, GF
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：
3.4
作者：
Chinopoulos, Christos;Vajda, Szilvia;Adam-Vizi, Vera
通讯作者：
Adam-Vizi, Vera