On the nature of ceramide-mitochondria interactions - Dissection using comprehensive mitochondrial phenotyping.

On the nature of ceramide-mitochondria interactions - Dissection using comprehensive mitochondrial phenotyping.
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关于神经酰胺-线粒体相互作用的性质-利用综合线粒体表型进行解剖。

DOI:
10.1016/j.cellsig.2020.109838
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发表时间:
2021-03
影响因子:
4.8
通讯作者:
Cabot MC
Cabot MC
中科院分区:
生物学2区
文献类型:
--
作者:
Fisher-Wellman KH;Hagen JT;Neufer PD;Kassai M;Cabot MC

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鞘脂是一类独特的脂质,这是由于其不含甘油的骨架神经酰胺,其由长链脂肪族氨基醇鞘氨醇构成,脂肪酸通过酰胺键连接到鞘氨醇上。神经酰胺通过与线粒体的相互作用在细胞凋亡的起始中起星星作用,线粒体是导致细胞凋亡的信号级联下游阵列的控制点。许多途径会聚在线粒体上以引起线粒体外膜透化(MOMP),这是破坏生物能量服务的一个步骤。虽然关于神经酰胺与线粒体的相互作用以及随后的细胞信号转导级联已经知道很多,但神经酰胺如何影响线粒体生物能量功能的元素却知之甚少。这篇综述的目的是向读者介绍鞘脂代谢,呈现线粒体呼吸的快照,详细说明神经酰胺在线粒体上的收敛以及协作引起MOMP的上游参与者,并介绍一个线粒体表型分析平台,该平台可以在解剖神经酰胺对细胞生物能量学的影响的细微之处中发挥作用。
Sphingolipids are a unique class of lipids owing to their non-glycerol-containing backbone, ceramide, that is constructed from a long-chain aliphatic amino alcohol, sphinganine, to which a fatty acid is attached via an amide bond. Ceramide plays a star role in the initiation of apoptosis by virtue of its interactions with mitochondria, a control point for a downstream array of signaling cascades culminating in apoptosis. Many pathways converge on mitochondria to elicit mitochondrial outer membrane permeabilization (MOMP), a step that corrupts bioenergetic service. Although much is known regarding ceramides interaction with mitochondria and the ensuing cell signal transduction cascades, how ceramide impacts the elements of mitochondrial bioenergetic function is poorly understood. The objective of this review is to introduce the reader to sphingolipid metabolism, present a snapshot of mitochondrial respiration, elaborate on ceramides convergence on mitochondria and the upstream players that collaborate to elicit MOMP, and introduce a mitochondrial phenotyping platform that can be of utility in dissecting the fine-points of ceramide impact on cellular bioenergetics.
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