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Novel mitochondrion‐targeting copper(II) complex induces HK2 malfunction and inhibits glycolysis via Drp1‐mediating mitophagy in HCC
by
Wang, Feixia
, Guo, Zijian
, Shao, Jiangjuan
, Jia, Yan
, Zhu, Zhenzhu
, Li, Mengmeng
, Jin, Chun
, Zheng, Shizhong
, Zhang, Ziji
, Wang, Xiaoyong
, Wang, Ling
, Zhang, Feng
in
Acidification
/ Acids
/ Animals
/ Autophagy
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - pathology
/ Coordination Complexes - chemical synthesis
/ Coordination Complexes - chemistry
/ Coordination Complexes - pharmacology
/ Copper
/ Copper - chemistry
/ copper complex
/ Dynamin
/ Dynamins - genetics
/ dynamin‐related protein 1
/ Gene Expression Regulation, Neoplastic - drug effects
/ Glucose
/ Glycolysis
/ Glycolysis - drug effects
/ Hepatoma
/ Heterografts
/ Hexokinase - antagonists & inhibitors
/ Hexokinase - genetics
/ hexokinase 2
/ Humans
/ Immunofluorescence
/ Immunoglobulins
/ Immunoprecipitation
/ Ligands
/ Lipophilic
/ Liver cancer
/ Liver Neoplasms - drug therapy
/ Liver Neoplasms - genetics
/ Liver Neoplasms - pathology
/ Medical research
/ Membrane permeability
/ Membrane potential
/ Metabolism
/ Metabolites
/ Mice
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - genetics
/ Mitochondria - pathology
/ Mitochondrial Dynamics - drug effects
/ Mitochondrial permeability transition pore
/ Mitophagy
/ Mitophagy - drug effects
/ Original
/ Physiology
/ Proteins
/ Transmission electron microscopy
/ Tumors
2020
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Novel mitochondrion‐targeting copper(II) complex induces HK2 malfunction and inhibits glycolysis via Drp1‐mediating mitophagy in HCC
by
Wang, Feixia
, Guo, Zijian
, Shao, Jiangjuan
, Jia, Yan
, Zhu, Zhenzhu
, Li, Mengmeng
, Jin, Chun
, Zheng, Shizhong
, Zhang, Ziji
, Wang, Xiaoyong
, Wang, Ling
, Zhang, Feng
in
Acidification
/ Acids
/ Animals
/ Autophagy
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - pathology
/ Coordination Complexes - chemical synthesis
/ Coordination Complexes - chemistry
/ Coordination Complexes - pharmacology
/ Copper
/ Copper - chemistry
/ copper complex
/ Dynamin
/ Dynamins - genetics
/ dynamin‐related protein 1
/ Gene Expression Regulation, Neoplastic - drug effects
/ Glucose
/ Glycolysis
/ Glycolysis - drug effects
/ Hepatoma
/ Heterografts
/ Hexokinase - antagonists & inhibitors
/ Hexokinase - genetics
/ hexokinase 2
/ Humans
/ Immunofluorescence
/ Immunoglobulins
/ Immunoprecipitation
/ Ligands
/ Lipophilic
/ Liver cancer
/ Liver Neoplasms - drug therapy
/ Liver Neoplasms - genetics
/ Liver Neoplasms - pathology
/ Medical research
/ Membrane permeability
/ Membrane potential
/ Metabolism
/ Metabolites
/ Mice
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - genetics
/ Mitochondria - pathology
/ Mitochondrial Dynamics - drug effects
/ Mitochondrial permeability transition pore
/ Mitophagy
/ Mitophagy - drug effects
/ Original
/ Physiology
/ Proteins
/ Transmission electron microscopy
/ Tumors
2020
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Novel mitochondrion‐targeting copper(II) complex induces HK2 malfunction and inhibits glycolysis via Drp1‐mediating mitophagy in HCC
by
Wang, Feixia
, Guo, Zijian
, Shao, Jiangjuan
, Jia, Yan
, Zhu, Zhenzhu
, Li, Mengmeng
, Jin, Chun
, Zheng, Shizhong
, Zhang, Ziji
, Wang, Xiaoyong
, Wang, Ling
, Zhang, Feng
in
Acidification
/ Acids
/ Animals
/ Autophagy
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - pathology
/ Coordination Complexes - chemical synthesis
/ Coordination Complexes - chemistry
/ Coordination Complexes - pharmacology
/ Copper
/ Copper - chemistry
/ copper complex
/ Dynamin
/ Dynamins - genetics
/ dynamin‐related protein 1
/ Gene Expression Regulation, Neoplastic - drug effects
/ Glucose
/ Glycolysis
/ Glycolysis - drug effects
/ Hepatoma
/ Heterografts
/ Hexokinase - antagonists & inhibitors
/ Hexokinase - genetics
/ hexokinase 2
/ Humans
/ Immunofluorescence
/ Immunoglobulins
/ Immunoprecipitation
/ Ligands
/ Lipophilic
/ Liver cancer
/ Liver Neoplasms - drug therapy
/ Liver Neoplasms - genetics
/ Liver Neoplasms - pathology
/ Medical research
/ Membrane permeability
/ Membrane potential
/ Metabolism
/ Metabolites
/ Mice
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - genetics
/ Mitochondria - pathology
/ Mitochondrial Dynamics - drug effects
/ Mitochondrial permeability transition pore
/ Mitophagy
/ Mitophagy - drug effects
/ Original
/ Physiology
/ Proteins
/ Transmission electron microscopy
/ Tumors
2020
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Novel mitochondrion‐targeting copper(II) complex induces HK2 malfunction and inhibits glycolysis via Drp1‐mediating mitophagy in HCC
Journal Article
Novel mitochondrion‐targeting copper(II) complex induces HK2 malfunction and inhibits glycolysis via Drp1‐mediating mitophagy in HCC
2020
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Overview
[Cu(ttpy‐tpp)Br2]Br (abbreviated as CTB) is a novel mitochondrion‐targeting copper(II) complex synthesized by our research group, which contains tri‐phenyl‐phosphonium (TPP) groups as its lipophilic property. In this study, we explored how CTB affects mitochondrial functions and exerts its anti‐tumour activity. Multiple functional and molecular analyses including Seahorse XF Bioanalyzer Platform, Western blot, immunofluorescence analysis, co‐immunoprecipitation and transmission electron microscopy were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo. We discovered that CTB inhibited aerobic glycolysis and cell acidification by impairing the activity of HK2 in hepatoma cells, accompanied by dissociation of HK2 from mitochondria. The modification of HK2 not only led to the complete dissipation of mitochondrial membrane potential (MMP) but also promoted the opening of mitochondrial permeability transition pore (mPTP), contributing to the activation of mitophagy. In addition, CTB co‐ordinately promoted dynamin‐related protein 1 (Drp1) recruitment in mitochondria to induce mitochondrial fission. Our findings established a previously unrecognized role for copper complex in aerobic glycolysis of tumour cells, revealing the interaction between mitochondrial HK2‐mediated mitophagy and Drp1‐regulated mitochondrial fission.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Acids
/ Animals
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - pathology
/ Coordination Complexes - chemical synthesis
/ Coordination Complexes - chemistry
/ Coordination Complexes - pharmacology
/ Copper
/ Dynamin
/ Gene Expression Regulation, Neoplastic - drug effects
/ Glucose
/ Hepatoma
/ Hexokinase - antagonists & inhibitors
/ Humans
/ Ligands
/ Liver Neoplasms - drug therapy
/ Mice
/ Mitochondrial Dynamics - drug effects
/ Mitochondrial permeability transition pore
/ Original
/ Proteins
/ Transmission electron microscopy
/ Tumors
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