Kadhim Ilham, Begum Nazneen, King William, Xu Licheng, Tang Fusheng
Department of Biology, University of Arkansas, Little Rock, AR 72204, USA.
Microb Cell. 2022 Jul 15;9(8):145-157. doi: 10.15698/mic2022.08.783. eCollection 2022 Aug 1.
Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between and , whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated complemented vacuolar morphology of Δ and enriched PI4P on the Golgi, indicating that Osh6 also works on the Golgi. This altered PI4P-enrichment led to a delay in the secretion of the proton ATPase Pma1 to the PM and a rerouting of Pma1 to vacuoles in a manner dependent on the trans-Golgi network (TGN) to late endosome (LE) trafficking pathway. Since the TGN-LE pathway controls endosomal and vacuolar TORC1, it may be the anti-aging pathway boosted by up-regulated Osh6.
氧甾醇结合蛋白家族成员介导膜之间的非囊泡脂质转运，并以不同方式促进长寿。我们之前发现，酵母七种氧甾醇结合蛋白之一的Osh6上调2倍可修复中年细胞中的液泡形态缺陷，部分下调雷帕霉素复合物1（TORC1）的靶点，并延长复制寿命。在分子水平上，Osh6在内质网（ER）和质膜（PM）之间转运磷脂酰丝氨酸（PS）和磷脂酰肌醇-4-磷酸（PI4P）。为了解析一种内质网-质膜工作蛋白如何控制液泡形态，我们测试了[此处原文缺失相关基因名称]与[此处原文缺失相关基因名称]之间的遗传相互作用，[此处原文缺失相关基因名称]的蛋白质将PS从高尔基体腔翻转到胞质侧，高尔基体是内质网和液泡之间在许多途径中的细胞器。上调的[此处原文缺失相关基因名称]补充了Δ[此处原文缺失相关基因名称]的液泡形态，并使高尔基体上的PI4P富集，表明Osh6也在高尔基体上起作用。这种改变的PI4P富集导致质子ATP酶Pma1向质膜的分泌延迟，并以依赖于反式高尔基体网络（TGN）到晚期内体（LE）的运输途径将Pma1重新导向液泡。由于TGN-LE途径控制内体和液泡TORC1，它可能是由上调的Osh6促进的抗衰老途径。
