Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), University of Witten/Herdecke (UW/H), Stockumer Str. 10, 58453 Witten, Germany.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
Cells. 2021 Sep 14;10(9):2416. doi: 10.3390/cells10092416.
Autophagy is a cellular recycling program which efficiently reduces the cellular burden of ageing. Autophagy is characterised by nucleation of isolation membranes, which grow in size and further expand to form autophagosomes, engulfing cellular material to be degraded by fusion with lysosomes (vacuole in yeast). Autophagosomal membranes do not bud from a single cell organelle, but are generated de novo. Several lipid sources for autophagosomal membranes have been identified, but the whole process of their generation is complex and not entirely understood. In this study, we investigated how the mitochondrial outer membrane protein porin 1 (Por1), the yeast orthologue of mammalian voltage-dependent anion channel (VDAC), affects autophagy in yeast. We show that deficiency reduces the autophagic capacity and leads to changes in vacuole and lipid homeostasis. We further investigated whether limited phosphatidylethanolamine (PE) availability in ∆ was causative for reduced autophagy by overexpression of the PE-generating phosphatidylserine decarboxylase 1 (Psd1). Altogether, our results show that deficiency is associated with reduced autophagy, which can be circumvented by additional overexpression. This suggests a role for Por1 in Psd1-mediated autophagy regulation.
自噬是一种细胞回收程序，可有效地减轻衰老带来的细胞负担。自噬的特征是隔离膜的成核，这些膜会增大并进一步扩展形成自噬体，吞噬待降解的细胞物质，然后与溶酶体（酵母中的液泡）融合。自噬体膜不会从单个细胞器中出芽，而是从头生成。已经确定了几种自噬体膜的脂质来源，但整个生成过程很复杂，并且不完全清楚。在这项研究中，我们研究了线粒体外膜蛋白孔蛋白 1（Por1）（哺乳动物电压依赖性阴离子通道（VDAC）的酵母同源物）如何影响酵母中的自噬。我们表明，Por1 缺失会降低自噬能力，并导致液泡和脂质稳态的变化。我们进一步研究了在 ∆ 中是否由于磷脂酰乙醇胺（PE）生成受限而导致自噬减少，方法是过表达产生 PE 的磷酸丝氨酸脱羧酶 1（Psd1）。总之，我们的结果表明，Por1 缺失与自噬减少有关，通过过表达额外的 Por1 可以避免这种情况。这表明 Por1 在 Psd1 介导的自噬调节中起作用。
