Klemm Robin W
Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
Contact (Thousand Oaks). 2021 Mar 3;4:2515256421993708. doi: 10.1177/2515256421993708. eCollection 2021 Jan-Dec.
Metabolic pathways are often spread over several organelles and need to be functionally integrated by controlled organelle communication. Physical organelle contact-sites have emerged as critical hubs in the regulation of cellular metabolism, but the molecular understanding of mechanisms that mediate formation or regulation of organelle interfaces was until recently relatively limited. Mitochondria are central organelles in anabolic and catabolic pathways and therefore interact with a number of other cellular compartments including the endoplasmic reticulum (ER) and lipid droplets (LDs). An interesting set of recent work has shed new light on the molecular basis forming these contact sites. This brief overview describes the discovery of unanticipated functions of contact sites between the ER, mitochondria and LDs in synthesis of storage lipids of brown and white adipocytes. Interestingly, the factors involved in mediating the interaction between these organelles are subject to unexpected modes of regulation through newly uncovered Phospho-FFAT motifs. These results suggest dynamic regulation of contact sites between organelles and indicate that spatial organization of organelles within the cell contributes to the control of metabolism.
代谢途径通常分布在多个细胞器中,需要通过受控的细胞器通讯进行功能整合。细胞器物理接触位点已成为细胞代谢调控的关键枢纽,但直到最近,对介导细胞器界面形成或调控机制的分子理解还相对有限。线粒体是合成代谢和分解代谢途径的核心细胞器,因此与包括内质网(ER)和脂滴(LDs)在内的许多其他细胞区室相互作用。最近一系列有趣的研究为形成这些接触位点的分子基础提供了新的线索。本简要概述描述了内质网、线粒体和脂滴之间接触位点在棕色和白色脂肪细胞储存脂质合成中意外功能的发现。有趣的是,介导这些细胞器之间相互作用的因子受到通过新发现的磷酸化 FFAT 基序的意外调控模式的影响。这些结果表明细胞器之间接触位点的动态调控,并表明细胞内细胞器的空间组织有助于代谢的控制。