Hypoxia‑induced mitochondrial translocation of DNM1L increases mitochondrial fission and triggers mPTP opening in HCC cells via activation of HK2 Retraction in /10.3892/or.2021.8059

Cai,Min; He,Ping; Fang,Dian‑Liang

doi:10.3892/or.2019.7213

Hypoxia‑induced mitochondrial translocation of DNM1L increases mitochondrial fission and triggers mPTP opening in HCC cells via activation of HK2

Retraction in: /10.3892/or.2021.8059

Authors:
- Min Cai
- Ping He
- Dian‑Liang Fang
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Affiliations: Department of Nephrology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China, Department of Gastroenterology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China
Published online on: June 27, 2019 https://doi.org/10.3892/or.2019.7213
Pages: 1125-1132

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Abstract

Disturbed mitochondrial dynamics are closely associated with the progression of different types of cancer including hepatocellular carcinoma (HCC). However, the manner in which mitochondrial dynamics are regulated in HCC remains largely unclear. In the present study, via immunofluorescence, real‑time PCR and western blot analysis, the effects of dynamin‑1‑like (DNM1L) on mitochondrial translocation and the mitochondrial permeability transition pore (mPTP) were investigated in HCC cells under hypoxic conditions, and the underlying molecular mechanisms were explored. Our data revealed that hypoxic treatment decreased the mitochondrial membrane potential, elevated generation of reactive oxygen species, and promoted mitochondrial fission in a DNM1L‑dependent manner. Instead of changing the levels of DNMlL, hypoxia increased the translocation of DNM1L to mitochondria, leading to excessive mitochondrial fission and decreased the viability of HCC cells. In addition to the effects on mitochondrial dynamics, DNM1L also regulated mPTP opening in HCC. IP analysis revealed that DNM1L interacted with the enzyme hexokinase 2 (HK2), and was involved in its phosphorylation, resulting in HK2 detachment from the mitochondria and consequently mPTP opening.

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