D'Angelo Donato, Vecellio Reane Denis, Raffaello Anna
Department of Biomedical Sciences, University of Padua, Padua, Italy.
Institute for Diabetes and Obesity, Helmholtz Zentrum München, Munich, Germany.
Front Mol Biosci. 2023 Dec 12;10:1336416. doi: 10.3389/fmolb.2023.1336416. eCollection 2023.
Ca ions serve as pleiotropic second messengers in the cell, regulating several cellular processes. Mitochondria play a fundamental role in Ca homeostasis since mitochondrial Ca (mitCa) is a key regulator of oxidative metabolism and cell death. MitCa uptake is mediated by the mitochondrial Ca uniporter complex (MCUc) localized in the inner mitochondrial membrane (IMM). MitCa uptake stimulates the activity of three key enzymes of the Krebs cycle, thereby modulating ATP production and promoting oxidative metabolism. As Paracelsus stated, "Dosis sola facit venenum,"in pathological conditions, mitCa overload triggers the opening of the mitochondrial permeability transition pore (mPTP), enabling the release of apoptotic factors and ultimately leading to cell death. Excessive mitCa accumulation is also associated with a pathological increase of reactive oxygen species (ROS). In this article, we review the precise regulation and the effectors of mitCa in physiopathological processes.
钙离子在细胞中作为多效性第二信使，调节多种细胞过程。线粒体在钙稳态中发挥着基本作用，因为线粒体钙（mitCa）是氧化代谢和细胞死亡的关键调节因子。MitCa的摄取由位于线粒体内膜（IMM）的线粒体钙单向转运体复合物（MCUc）介导。MitCa的摄取刺激了三羧酸循环中三种关键酶的活性，从而调节ATP的产生并促进氧化代谢。正如帕拉塞尔苏斯所说：“剂量决定毒性”，在病理条件下，mitCa过载会触发线粒体通透性转换孔（mPTP）的开放，使凋亡因子释放，最终导致细胞死亡。过量的mitCa积累还与活性氧（ROS）的病理性增加有关。在本文中，我们综述了mitCa在生理病理过程中的精确调节及其效应器。
