Schlarmann Philipp, Ikeda Atsuko, Funato Kouichi
Graduate School of Integrated Sciences for Life, Hiroshima University, Kagamiyama 1-4-4, Higashi-Hiroshima 739-8528, Japan.
Membranes (Basel). 2021 Dec 9;11(12):971. doi: 10.3390/membranes11120971.
Sphingolipids are the most diverse class of membrane lipids, in terms of their structure and function. Structurally simple sphingolipid precursors, such as ceramides, act as intracellular signaling molecules in various processes, including apoptosis, whereas mature and complex forms of sphingolipids are important structural components of the plasma membrane. Supplying complex sphingolipids to the plasma membrane, according to need, while keeping pro-apoptotic ceramides in check is an intricate task for the cell and requires mechanisms that tightly control sphingolipid synthesis, breakdown, and storage. As each of these processes takes place in different organelles, recent studies, using the budding yeast , have investigated the role of membrane contact sites as hubs that integrate inter-organellar sphingolipid transport and regulation. In this review, we provide a detailed overview of the findings of these studies and put them into the context of established regulatory mechanisms of sphingolipid homeostasis. We have focused on the role of membrane contact sites in sphingolipid metabolism and ceramide transport, as well as the mechanisms that prevent toxic ceramide accumulation.
就结构和功能而言，鞘脂是种类最多样化的膜脂类别。结构简单的鞘脂前体，如神经酰胺，在包括细胞凋亡在内的各种过程中充当细胞内信号分子，而成熟和复杂形式的鞘脂是质膜的重要结构成分。根据需要向质膜供应复杂鞘脂，同时控制促凋亡神经酰胺，这对细胞来说是一项复杂的任务，需要严格控制鞘脂合成、分解和储存的机制。由于这些过程中的每一个都发生在不同的细胞器中，最近利用芽殖酵母进行的研究调查了膜接触位点作为整合细胞器间鞘脂运输和调节中心的作用。在这篇综述中，我们详细概述了这些研究的结果，并将它们置于鞘脂稳态既定调节机制的背景下。我们重点关注了膜接触位点在鞘脂代谢和神经酰胺运输中的作用，以及防止有毒神经酰胺积累的机制。
