Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions.
Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions.
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线粒体通透性转换孔的身份，结构和功能：争议，共识，最近的进展和未来的方向。
DOI：
10.1038/s41418-023-01187-0
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发表时间：
2023-08
影响因子：
12.4
通讯作者：
Soukas AA
中科院分区：
文献类型：
--
作者：
Bernardi P;Gerle C;Halestrap AP;Jonas EA;Karch J;Mnatsakanyan N;Pavlov E;Sheu SS;Soukas AA
线粒体渗透性转换（mPT）描述了一种Ca 2+依赖性和亲环素D（CypD）促进的线粒体内膜渗透性增加，允许分子扩散至1.5 kDa的大小。它是由一个非选择性通道，线粒体通透性转换孔（mPTP）介导的。持续的mPTP开放导致线粒体肿胀，其使线粒体外膜破裂，导致随后的凋亡和坏死细胞死亡，并且涉及一系列病理学。然而，在各种亚电导状态下的瞬时mPTP开放可能有助于几种生理作用，如线粒体生物能量学和快速Ca 2+流出的改变。自几十年前发现以来，人们一直在努力确定mPT的确切成孔结构。腺嘌呤核苷酸移位酶（ANT）和最近的线粒体F1 FO（F）-ATP合酶二聚体、单体或单独的c-亚基环都涉及。在这里，我们分享了几位具有不同观点的关键研究人员的见解，他们是mPT研究的先驱。我们批判性地评估提出的模型的mPTP的分子身份和其在细胞的生命和死亡的相反作用的机制。我们对当前的争议提供了深入的见解，寻求达成一定程度的共识，这将刺激未来对mPTP的性质和作用的创新研究。
The mitochondrial permeability transition (mPT) describes a Ca2+-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca2+ efflux. Since its discovery decades ago, intensive efforts have been made to identify the exact pore-forming structure of the mPT. Both the adenine nucleotide translocase (ANT) and, more recently, the mitochondrial F1FO (F)-ATP synthase dimers, monomers or c-subunit ring alone have been implicated. Here we share the insights of several key investigators with different perspectives who have pioneered mPT research. We critically assess proposed models for the molecular identity of the mPTP and the mechanisms underlying its opposing roles in the life and death of cells. We provide in-depth insights into current controversies, seeking to achieve a degree of consensus that will stimulate future innovative research into the nature and role of the mPTP.
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影响因子：
4.3
作者：
Bonora, Massimo;Bononi, Angela;Pinton, Paolo
通讯作者：
Pinton, Paolo
影响因子：
9.5
作者：
Baines CP
通讯作者：
Baines CP
线粒体闪光：细胞和细胞器生物学中的综合活性氧和 pH 信号
影响因子：
6.6
作者：
Wang W;Gong G;Wang X;Wei-LaPierre L;Cheng H;Dirksen R;Sheu SS
通讯作者：
Sheu SS
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
3
作者：
BERNARDI, P;BROEKEMEIER, KM;PFEIFFER, DR
通讯作者：
PFEIFFER, DR