Liver-specific loss of Atg9a perturbs lipid metabolism and hepatocyte integrity.

Autophagy reports Pub Date : 2025-09-02 eCollection Date: 2025-01-01 DOI:10.1080/27694127.2025.2551028
Elodie Mailler, Asmita Singh, Michal Jarnik, Yan Li, Lynne Holtzclaw, Victoria Hoffmann, Sohtaro Mine, Paulina Stallcup, Laleh Ordoubadinia, Carlos M Guardia
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Abstract

The autophagy-related protein ATG9A is integral to cellular autophagy and lipid mobilization, yet its importance in mammalian physiology remains underexplored. Using a liver-specific conditional Atg9a knockout (Atg9a-cKO) mouse model, we uncovered critical insights into the physiological function of ATG9A in this organ. Atg9a-cKO mice exhibited hepatomegaly, abnormal hepatocyte morphology, mitochondrial fragmentation, and lipid droplet accumulation. Blood chemistry and proteomics analyses revealed elevated serum cholesterol, reduced albumin, and dysregulation of pathways related to lipid metabolism and oxidative stress responses. These findings establish an essential role for ATG9A in maintaining hepatocyte integrity, lipid trafficking, and overall liver health, offering a model for studying autophagy-related hepatic pathologies.

肝脏特异性Atg9a缺失会扰乱脂质代谢和肝细胞完整性。
自噬相关蛋白ATG9A是细胞自噬和脂质动员不可或缺的一部分,但其在哺乳动物生理学中的重要性仍未得到充分探讨。使用肝脏特异性条件Atg9a敲除(Atg9a- cko)小鼠模型,我们揭示了Atg9a在该器官中的生理功能的关键见解。Atg9a-cKO小鼠表现为肝肿大、肝细胞形态异常、线粒体断裂和脂滴积聚。血液化学和蛋白质组学分析显示血清胆固醇升高,白蛋白减少,脂质代谢和氧化应激反应相关途径失调。这些发现确立了ATG9A在维持肝细胞完整性、脂质运输和整体肝脏健康方面的重要作用,为研究自噬相关的肝脏病理提供了一个模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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