Cyclophilin D regulates neuronal activity-induced filopodiagenesis by fine-tuning dendritic mitochondrial calcium dynamics.
Cyclophilin D regulates neuronal activity-induced filopodiagenesis by fine-tuning dendritic mitochondrial calcium dynamics.
复制标题
DOI：
10.1111/jnc.14484
复制
发表时间：
2018-08
影响因子：
4.7
通讯作者：
Du H
中科院分区：
文献类型：
--
作者：
Sui S;Tian J;Gauba E;Wang Q;Guo L;Du H
Recent studies have highlighted the role of mitochondria in dendritic protrusion growth and plasticity. However, the detailed mechanisms that mitochondria regulate dendritic filopodia morphogenesis remain elusive. Cyclophilin D (CypD, gene name: Ppif) controls the opening of mitochondrial permeability transition pore (mPTP). Although the pathological relevance of CypD has been intensively investigated, little is known about its physiological function in neurons. Here, we have found that genetic depletion of or pharmaceutical inhibiton of CypD blunts the outgrowth of dendritic filopodia in response to KCl-stimulated neuronal depolarization. Further cell biological studies suggest that such inhibitory effect of CypD loss-of-function is closely associated with compromised flexibility of dendritic mitochondrial calcium regulation during neuronal depolarization, as well as the resultant changes in intra-dendritic calcium homeostasis, calcium signaling activation, dendritic mitochondrial motility and redistribution. Interestingly, loss of CypD attenuates oxidative stress-induced mitochondrial calcium perturbations and dendritic protrusion injury. Therefore, our study has revealed the physiological function of CypD in dendritic plasticity by acting as a fine-tuner of mitochondrial calcium homeostasis. Moreover, CypD plays distinct roles in neuronal physiology and pathology. Dendritic spinogenesis are energy demanding and regulated by local calcium transients. Cyclophilin D (CypD)-mediated mitochondrial permeability transition (mPT) is a critical pathway for mitochondrial release. But whether CypD-medaited mPTP contributes to neuronal activity-induced dendritic spinogenesis is unknown. Here, we have found that transient opening of CypD-mediated (mPTP) regulates intra-dendritic calcium dynamics by mediating mitochondrial calcium release and the downstream signaling, eventually promoting activity-induced dendritic protrusion outgrowth. This phenomenon highlights the role of CypD in neuronal physiology and implicates the limitation of CypD inhibition as a preventive strategy for diseases.
登录
查看更多内容
影响因子：
8.8
作者：
Kwong JQ;Lu X;Correll RN;Schwanekamp JA;Vagnozzi RJ;Sargent MA;York AJ;Zhang J;Bers DM;Molkentin JD
通讯作者：
Molkentin JD
DOI：
10.1111/j.1460-9568.2010.07576.x
发表时间：
2011-03
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Barsukova A;Komarov A;Hajnóczky G;Bernardi P;Bourdette D;Forte M
通讯作者：
Forte M
DOI：
10.1073/pnas.1006586107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Du, Heng;Guo, Lan;Yan, Shirley ShiDu
通讯作者：
Yan, Shirley ShiDu
影响因子：
5.3
作者：
Kovács, R;Kardos, J;Kann, O
通讯作者：
Kann, O
影响因子：
7.7
作者：
Giorgio, Valentina;Burchell, Victoria;Bernardi, Paolo
通讯作者：
Bernardi, Paolo