Cadmium promotes nonalcoholic fatty liver disease by inhibiting intercellular mitochondrial transfer

Cellular & Molecular Biology Letters

Research Article

Zongping Liu¹  Jianchun Bian¹  Hui Zou¹  Waseem Ali¹  Jian Sun¹  Yan Chen¹  Yonggang Ma¹  Jianhong Gu¹  Tao Wang¹  Yan Yuan¹ 

[1]College of Veterinary Medicine, Yangzhou University, Yangzhou, China

[2]Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China

关键词: Cadmium;    Intercellular mitochondrial transfer;    Tunneling nanotubes;    Nonalcoholic fatty liver disease;   

DOI  :  10.1186/s11658-023-00498-x

 received in 2023-05-18, accepted in 2023-10-10,  发布年份 2023

来源: Springer

【 摘 要 】

Mitochondrial transfer regulates intercellular communication, and mitochondria regulate cell metabolism and cell survival. However, the role and mechanism of mitochondrial transfer in Cd-induced nonalcoholic fatty liver disease (NAFLD) are unclear. The present study shows that mitochondria can be transferred between hepatocytes via microtubule-dependent tunneling nanotubes. After Cd treatment, mitochondria exhibit perinuclear aggregation in hepatocytes and blocked intercellular mitochondrial transfer. The different movement directions of mitochondria depend on their interaction with different motor proteins. The results show that Cd destroys the mitochondria-kinesin interaction, thus inhibiting mitochondrial transfer. Moreover, Cd increases the interaction of P62 with Dynactin1, promotes negative mitochondrial transport, and increases intracellular lipid accumulation. Mitochondria and hepatocyte co-culture significantly reduced Cd damage to hepatocytes and lipid accumulation. Thus, Cd blocks intercellular mitochondrial transfer by disrupting the microtubule system, inhibiting mitochondrial positive transport, and promoting their negative transport, thereby promoting the development of NAFLD.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 9

41512_2023_158_Article_IEq26.gif

Fig. 1

Fig. 7

Fig. 9

Fig. 7

Fig. 3

Fig. 2

12944_2023_1932_Article_IEq4.gif