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

作者信息

Mailler Elodie, Singh Asmita, Jarnik Michal, Li Yan, Holtzclaw Lynne, Hoffmann Victoria, Mine Sohtaro, Stallcup Paulina, Ordoubadinia Laleh, Guardia Carlos M

机构信息

Division of Neurosciences & Cellular Structure, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Placental Cell Biology Group, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.

出版信息

Autophagy Rep. 2025 Sep 2;4(1):2551028. doi: 10.1080/27694127.2025.2551028. eCollection 2025.

DOI:10.1080/27694127.2025.2551028
PMID:40910069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12408054/
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 knockout (-cKO) mouse model, we uncovered critical insights into the physiological function of ATG9A in this organ. -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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/635bfac5e4df/KAUO_A_2551028_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/4117ee6a7932/KAUO_A_2551028_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/0caf70322f3b/KAUO_A_2551028_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/0d6aa7178567/KAUO_A_2551028_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/3d3b33231677/KAUO_A_2551028_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/125d872f29d1/KAUO_A_2551028_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/06da899812b5/KAUO_A_2551028_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/635bfac5e4df/KAUO_A_2551028_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/4117ee6a7932/KAUO_A_2551028_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/0caf70322f3b/KAUO_A_2551028_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/0d6aa7178567/KAUO_A_2551028_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/3d3b33231677/KAUO_A_2551028_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/125d872f29d1/KAUO_A_2551028_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/06da899812b5/KAUO_A_2551028_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/12408054/635bfac5e4df/KAUO_A_2551028_F0007_OC.jpg

相似文献

[1]
Liver-specific loss of perturbs lipid metabolism and hepatocyte integrity.

Autophagy Rep. 2025-9-2

[2]
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology.

Autophagy. 2024-11

[3]
RHOD mediates ATG9A trafficking to promote autophagosome formation during autophagy in cancer.

Autophagy. 2025-4-1

[4]
GRINA alleviates hepatic ischemia‒reperfusion injury-induced apoptosis and ER-phagy by enhancing HRD1-mediated ATF6 ubiquitination.

J Hepatol. 2025-1-22

[5]
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Cell Commun Signal. 2025-7-1

[6]
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Autophagy. 2025-3-21

[7]
ATG9A controls all stages of autophagosome biogenesis.

Autophagy. 2025-4-27

[8]
Reduced expression of gene in cortex glia causes dopaminergic cell death.

J Parkinsons Dis. 2025-8

[9]
A missense variant in human perilipin 2 ( Ser251Pro) reduces hepatic steatosis in mice.

JHEP Rep. 2023-10-11

[10]
Aldh1l2 knockout mouse metabolomics links the loss of the mitochondrial folate enzyme to deregulation of a lipid metabolism observed in rare human disorder.

Hum Genomics. 2020-11-9

本文引用的文献

[1]
Identification of necroptosis-related gene expression and the immune response in polycystic ovary syndrome.

J Assist Reprod Genet. 2024-12

[2]
Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma.

iScience. 2023-10-30

[3]
ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A.

Autophagy. 2024-3

[4]
Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation.

J Cell Biol. 2023-7-3

[5]
The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury.

Int J Mol Sci. 2023-2-4

[6]
Autophagy genes in biology and disease.

Nat Rev Genet. 2023-6

[7]
Orchestration of selective autophagy by cargo receptors.

Curr Biol. 2022-12-19

[8]
Many roads lead to CASM: Diverse stimuli of noncanonical autophagy share a unifying molecular mechanism.

Sci Adv. 2022-10-28

[9]
Mitochondrial alterations in fatty liver diseases.

J Hepatol. 2023-2

[10]
In situ structural analysis reveals membrane shape transitions during autophagosome formation.

Proc Natl Acad Sci U S A. 2022-9-27

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