PDF(Pubmed)
Abstract：
Mitochondria are dynamic organelles that undergo cycles of fission and fusion at a unified platform defined by endoplasmic reticulum (ER)-mitochondria membrane contact sites (MCSs). These MCSs or nodes co-localize fission and fusion machinery. We set out to identify how ER-associated mitochondrial nodes can regulate both fission and fusion machinery assembly. We have used a promiscuous biotin ligase linked to the fusion machinery, Mfn1, and proteomics to identify an ER membrane protein, ABHD16A, as a major regulator of node formation. In the absence of ABHD16A, fission and fusion machineries fail to recruit to ER-associated mitochondrial nodes, and fission and fusion rates are significantly reduced. ABHD16A contains an acyltransferase motif and an α/β hydrolase domain, and point mutations in critical residues of these regions fail to rescue the formation of ER-associated mitochondrial hot spots. These data suggest a mechanism whereby ABHD16A functions by altering phospholipid composition at ER-mitochondria MCSs. Our data present the first example of an ER membrane protein that regulates the recruitment of both fission and fusion machineries to mitochondria.
摘要：
线粒体是动态的细胞器，在由内质网（ER）-线粒体膜接触位点（MCSs）定义的统一平台上进行裂变和融合循环。这些MCS或节点共同定位裂变和聚变机制。我们着手确定ER相关的线粒体节点如何调节裂变和融合机器组装。我们使用了一种与融合机制相连的混杂生物素连接酶，Mfn1和蛋白质组学鉴定ER膜蛋白，ABHD16A,作为节点形成的主要调节器。在没有ABHD16A的情况下，裂变和融合机制无法招募到ER相关的线粒体节点，裂变和聚变率显著降低。ABHD16A包含一个酰基转移酶基序和一个α/β水解酶结构域，这些区域的关键残基中的点突变无法挽救ER相关线粒体热点的形成。这些数据表明ABHD16A通过改变ER-线粒体MCSs处的磷脂组成而起作用的机制。我们的数据提供了ER膜蛋白的第一个例子，该蛋白调节裂变和融合机制向线粒体的募集。
