Melani Mariana, Valko Ayelén, Romero Nuria M, Aguilera Milton O, Acevedo Julieta M, Bhujabal Zambarlal, Perez-Perri Joel, de la Riva-Carrasco Rocío V, Katz Maximiliano J, Sorianello Eleonora, D'Alessio Cecilia, Juhász Gabor, Johansen Terje, Colombo María I, Wappner Pablo
Fundación Instituto Leloir, Buenos Aires 1405, Argentina.
Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
Mol Biol Cell. 2017 Nov 1;28(22):3070-3081. doi: 10.1091/mbc.E16-11-0767. Epub 2017 Sep 13.
Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions and, soon after starvation, nucleates in endoplasmic reticulum-associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13, and Atg17 but does not require Vps34, Vps15, Atg6, or Atg14. Zonda interacts physically with Atg1 through its kinase domain, as well as with Atg6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.
自噬是一种进化上保守的过程,真核细胞通过该过程对细胞质成分进行自我消化。在此我们报告,一种新型亲免素(我们将其命名为Zonda)对于饥饿诱导的自噬至关重要。我们表明,Zonda在该过程的早期阶段发挥作用,特别是对于Vps34介导的磷脂酰肌醇3-磷酸(PI3P)沉积。Zonda在基础条件下呈均匀分布,饥饿后不久,在内质网相关的病灶中形成核,这些病灶与omegasome标记物共定位。Zonda的成核依赖于Atg1、Atg13和Atg17,但不需要Vps34、Vps15、Atg6或Atg14。Zonda通过其激酶结构域与Atg1以及与Atg6和Vps34发生物理相互作用。我们提出,Zonda是自噬级联反应的早期成分,对于Vps34依赖性PI3P沉积和omegasome形成是必需的。