Details

Autor(en) / Beteiligte

• Che, Lin
• Huang, Jing
• Lin, Jin-Xian
• Xu, Chi-Yu
• Wu, Xin-Mou
• Du, Ze-Bang
• Wu, Jia-Shen
• Lin, Zhong-Ning
• Lin, Yu-Chun

Titel

Aflatoxin B1 exposure triggers hepatic lipotoxicity via p53 and perilipin 2 interaction-mediated mitochondria-lipid droplet contacts: An in vitro and in vivo assessment

Ist Teil von

• Journal of hazardous materials, 2023-03, Vol.445, p.130584-130584, Article 130584

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins widely found in food contaminants, and its target organ is the liver. It poses a major food security and public health threat worldwide. However, the lipotoxicity mechanism of AFB1 exposure-induced liver injury remains unclear and requires further elucidation. Herein, we investigated the potential hepatic lipotoxicity of AFB1 exposure using in vitro and in vivo models to assess the public health hazards of high dietary AFB1 exposure. We demonstrated that low-dose of AFB1 (1.25 μM for 48 h, about one-fifth of the IC50 in HepG2 and HepaRG cells, IC50 are 5.995 μM and 5.266 μM, respectively) exposure significantly induced hepatic lipotoxicity, including abnormal lipid droplets (LDs) growth, mitochondria-LDs contacts increase, lipophagy disruption, and lipid accumulation. Mechanistically, we showed that AFB1 exposure promoted the mitochondrial p53 (mito-p53) and LDs-associated protein perilipin 2 (PLIN2) interaction-mediated mitochondria-LDs contacts, resulting in lipid accumulation in hepatocytes. Mito-p53-targeted inhibition, knockdown of PLIN2, and rapamycin application efficiently promoted the lysosome-dependent lipophagy and alleviated the hepatic lipotoxicity and liver injury induced by AFB1 exposure. Overall, our study found that mito-p53 and PLIN2 interaction mediates three organelles-mitochondria, LDs, and lysosomal networks to regulate lipid homeostasis in AFB1 exposure-induced hepatotoxicity, revealing how this unique trio of organelles works together and provides a novel insight into the targeted intervention in inter-organelle lipid sensing and trafficking for alleviating hazardous materials-induced hepatic lipotoxicity. [Display omitted] •Aflatoxin B1 (AFB1) exposure-induced inter-organelle lipid trafficking mediates hepatic lipotoxicity.•Mito-p53 and perilipin 2 interaction mediates mitochondria and lipid droplets (LDs) communication.•AFB1 exposure promotes LDs growth via inhibiting lysosome-associated lipophagy.•Targeted intervention on mito-p53 alleviates AFB1-induced hepatic lipotoxicity and liver injury.