Ceramide-induced autophagy: to junk or to protect cells?
Ceramide-induced autophagy: to junk or to protect cells?
复制标题
DOI：
10.4161/auto.5.4.8390
复制
发表时间：
2009-05
期刊：
影响因子：
13.3
通讯作者：
Codogno P
中科院分区：
文献类型：
--
作者：
Pattingre S;Bauvy C;Levade T;Levine B;Codogno P
神经酰胺是一种鞘脂生物活性分子，可诱导细胞凋亡和其他形式的细胞死亡，并引发巨自噬（以下简称自噬）。与氨基酸饥饿一样，神经酰胺通过干扰 mTOR 信号通路以及以 c-Jun N 末端激酶 1 (JNK1) 介导的 Bcl-2 磷酸化依赖性方式解离 Beclin 1:Bcl-2 复合物来触发自噬。在长链神经酰胺的细胞水平增加的各种情况下都观察到了 Beclin 1:Bcl-2 复合物的解离以及随后的自噬刺激。值得注意的是，短链神经酰胺（C2-神经酰胺和C6-神经酰胺）通过神经酰胺合酶的活性转化为长链神经酰胺是触发自噬所必需的。还观察到 Beclin 1:Bcl-2 复合物的解离是对他莫昔芬和 PDMP（一种将神经酰胺转化为葡萄糖神经酰胺的酶的抑制剂）的反应，这两种药物可增加细胞内长链神经酰胺的水平。然而，与饥饿相反，Bcl-2 的过度表达不会减弱神经酰胺诱导的自噬。这种不受 Beclin 1:Bcl-2 复合物强制解离抑制的自噬是否与神经酰胺触发细胞死亡的能力有关仍然是一个悬而未决的问题。更一般地说，神经酰胺诱导的自噬是否是一种专门的细胞死亡机制的问题值得更仔细的审查。
Ceramide is a sphingolipid bioactive molecule that induces apoptosis and other forms of cell death, and triggers macroautophagy (referred to below as autophagy). Like amino acid starvation, ceramide triggers autophagy by interfering with the mTOR-signaling pathway, and by dissociating the Beclin 1:Bcl-2 complex in a c-Jun N-terminal kinase 1 (JNK1)-mediated Bcl-2 phosphorylation-dependent manner. Dissociation of the Beclin 1:Bcl-2 complex, and the subsequent stimulation of autophagy have been observed in various contexts in which the cellular level of long-chain ceramides was increased. It is notable that the conversion of short-chain ceramides (C2-ceramide and C6-ceramide) into long-chain ceramide via the activity of ceramide synthase is required to trigger autophagy. The dissociation of the Beclin 1:Bcl-2 complex has also been observed in response to tamoxifen and PDMP (an inhibitor of the enzyme that converts ceramide to glucosylceramide), drugs that increase the intracellular level of long-chain ceramides. However, and in contrast to starvation, over-expression of Bcl-2 does not blunt ceramide-induced autophagy. Whether this autophagy that is unchecked by forced dissociation of the Beclin 1:Bcl-2 complex is related to the ability of ceramide to trigger cell death remains an open question. More generally, the question of whether ceramide-induced autophagy is a dedicated cell death mechanism deserves closer scrutiny.
登录
查看更多内容
影响因子：
5.7
作者：
Samaddar, Julia S.;Gaddy, Virgil T.;Schoenlein, Patricia V.
通讯作者：
Schoenlein, Patricia V.
影响因子：
4.8
作者：
Pattingre, Sophie;Bauvy, Chantal;Codogno, Patrice
通讯作者：
Codogno, Patrice
影响因子：
4.8
作者：
Scarlatti, F;Bauvy, C;Codogno, P
通讯作者：
Codogno, P
影响因子：
4.8
作者：
Lavieu, G;Scarlatti, F;Codogno, P
通讯作者：
Codogno, P
影响因子：
11.2
作者：
Daido, S;Kanzawa, T;Kondo, S
通讯作者：
Kondo, S