LKB1/AMPKα signaling pathway and mitochondrial fission/fusion dynamics regulate apoptosis induced by 3-chlorpropane-1,2-diol in HEK293 cells

• Published in: Food and chemical toxicology 2021-08, Vol.154, p.112350, Article 112350
• Main Authors: Jin, Chengni, Xue, Wei, Liu, Qi, Han, Jiahui, Luo, Ruilin, Feng, Jiayu, Liu, Jiayu, Guo, Tianmin, Peng, Xiaoli, Hu, Tianming
• Format: Article
• Language: English
• Subjects: 3-Chlorpropane-1,2-diol (3-MCPD); AMPK; Apoptosis; Mitochondrial dysfunction; Mitochondrial fission
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112350

Mitochondrial dynamics and bioenergetics are considered play pivotal roles in the maintenance of mitochondrial function and cell viability. During the widely distributed food contaminant 3-chlorpropane-1,2-diol (3-MCPD) induced nephrotoxicity, mitochondrial morphology and function were impaired, but the specific mechanism responsible for the process has not been fully elucidated. In the present study, using an in vitro human embryonic kidney 293 (HEK293) cell culture model, the role of LKB1/AMPK pathway and mitochondrial fission and fusion dynamics in 3-MCPD-induced cell apoptosis was investigated by using the AMPK inhibitor dorsomorphin and mitochondrial division inhibitor 1 (Mdivi-1), respectively. The results revealed that 3-MCPD significantly decreased the ATP levels, activated the energy-sensing regulator AMPKα and its upstream protein kinase LKB1, disrupted mitochondrial dynamics equilibrium characterized by promoting division and inhibiting fusion, thus inducing cell apoptosis. Notably, suppression of AMPK by dorsomorphin mitigated 3-MCPD-induced cytotoxicity through improvement of the function and dynamics of mitochondria and alleviated apoptosis via the mitochondria-dependent pathway. Moreover, inhibition of mitochondrial fission by Mdivi-1 protected against apoptosis induced by 3-MCPD. Taken together, these results suggest that 3-MCPD triggers apoptosis through activation of LKB1/AMPKα signaling pathway and regulation of mitochondrial fission and fusion dynamics in HEK293 cells. [Display omitted] •3-MCPD activated LKB1/AMPKα signaling pathway in human embryonic kidney cells.•Suppression of AMPK improved the function and dynamics of mitochondria and alleviated 3-MCPD-evoked renal cell damage.•3-MCPD led to mitochondrial fusion and fission dynamics disorder.•Inhibition of mitochondrial fission protected against 3-MCPD-induced apoptosis via the mitochondria-dependent pathway.