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Inorganic polyphosphate is required for sustained free mitochondrial calcium elevation, following calcium uptake.
Cell Calcium ( IF 4.3 ) Pub Date : 2019-12-09 , DOI: 10.1016/j.ceca.2019.102127
Maria E Solesio 1 , Luis C Garcia Del Molino 2 , Pia A Elustondo 3 , Catherine Diao 4 , Joshua C Chang 5 , Evgeny V Pavlov 1
Affiliation  

Mitochondrial free calcium is critically linked to the regulation of cellular metabolism. Free ionic calcium concentration within these organelles is determined by the interplay between two processes: exchange across the mitochondrial inner membrane and calcium-buffering within the matrix. During stimulated calcium uptake, calcium is primarily buffered by orthophosphate, preventing calcium toxicity while allowing for well-regulated yet elevated calcium loads. However, if limited to orthophosphates only, this buffering system is expected to lead to the irreversible formation of insoluble precipitates, which are not observed in living cells, under physiological conditions. Here, we demonstrate that the regulation of free mitochondrial calcium requires the presence of free inorganic polyphosphate (polyP) within the organelle. We found that the overexpression of a mitochondrial-targeted enzyme hydrolyzing polyP leads to the loss of the cellular ability to maintain elevated calcium concentrations within the organelle, following stimulated cytoplasmic signal. We hypothesize that the presence of polyP prevents the formation of calcium-phosphate insoluble clusters, allowing for the maintenance of elevated free calcium levels, during stimulated calcium uptake.

中文翻译:


钙吸收后,无机多磷酸盐是维持线粒体游离钙持续升高所必需的。



线粒体游离钙与细胞代谢的调节密切相关。这些细胞器内的游离离子钙浓度由两个过程之间的相互作用决定:线粒体内膜的交换和基质内的钙缓冲。在刺激钙吸收过程中,钙主要由正磷酸盐缓冲,防止钙毒性,同时允许良好调节但升高的钙负荷。然而,如果仅限于正磷酸盐,则该缓冲系统预计会导致不可逆形成不溶性沉淀物,而在生理条件下,在活细胞中观察不到这种沉淀物。在这里,我们证明游离线粒体钙的调节需要细胞器内存在游离无机多磷酸盐(polyP)。我们发现,在受到刺激的细胞质信号后,线粒体靶向酶水解聚P的过度表达会导致细胞丧失维持细胞器内钙浓度升高的能力。我们假设,polyP 的存在可以防止磷酸钙不溶簇的形成,从而在刺激钙吸收过程中维持较高的游离钙水平。
更新日期:2019-12-09
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