The oxidoreductase CLIC4 is required to maintain mitochondrial function and resistance to exogenous oxidants in breast cancer cells

Khamici, Heba Al; Sanchez, Vanesa C.; Yan, Hualong; Cataisson, Christophe; Yang, Howard; Li, Luowei; Lee, Maxwell P.; Huang, Jing; Yuspa, Stuart H.

doi:10.1016/j.jbc.2022.102275

Cited by 3 publications

(4 citation statements)

References 81 publications

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“…For example, the accumulation of cellular ROS, as a signaling module, was increased by deleting CLIC4 from murine 6DT1 breast tumor cells Frontiers in Physiology frontiersin.org using CRISPR (Al Khamici et al, 2022). Similarly, the decreased intracellular MMP in the study after TnCLIC knockdown in Hi-5 cells suggests that TnCLIC may play a pivotal role in the maintenance of mitochondrial function.…”

Section: Discussionmentioning

confidence: 86%

“…Since mitochondrial depolarization ( Lu et al, 2018 ) and reactive oxidative stress (ROS) ( Kiselyov and Muallem, 2016 ) play a highly relevant role in apoptosis by modulating of mammalian CLICs, mitochondrial membrane potential (MMP) and ROS generation are thus commonly used to gain a better understanding of their function. For example, the accumulation of cellular ROS, as a signaling module, was increased by deleting CLIC4 from murine 6DT1 breast tumor cells using CRISPR ( Al Khamici et al, 2022 ). Similarly, the decreased intracellular MMP in the study after TnCLIC knockdown in Hi-5 cells suggests that Tn CLIC may play a pivotal role in the maintenance of mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

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Chloride intracellular channel gene knockdown induces insect cell lines death and level increases of intracellular calcium ions

Song

Yan

et al. 2023

Front. Physiol.

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Chloride intracellular channel (CLIC) is a member of the chloride channel protein family for which growing evidence supports a pivotal role in fundamental cellular events. However, the physiological function of CLIC in insects is still rarely uncovered. The ovary-derived High Five (Hi-5) cell line isolated from the cabbage looper (Trichoplusia ni) is widely used in laboratories. Here, we studied both characteristics and functions of CLIC in Hi-5 cells (TnCLIC). We identified the TnCLIC gene in Hi-5 cells and annotated highly conserved CLIC proteins in most insect species. After RNA interference of TnCLIC, the phenomenon of significantly increased cell death suggests that the TnCLIC protein is essential for the survival of Hi-5 cells. The same lethal effect was also observed in Spodoptera frugiperda 9 and Drosophila melanogaster Schneider 2 cells after CLIC knockdown. Furthermore, we found that this kind of cell death was accompanied by increases in intracellular calcium ions after TnCLIC knockdown with the transcriptomic analyses and the detection of calcium levels. Our results provide insights into insect CLIC as a key factor for cell survival and lay the foundation for the cell death mechanism.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Chloride intracellular channel gene knockdown induces insect cell lines death and level increases of intracellular calcium ions

Song

Yan

et al. 2023

Front. Physiol.

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“…These results showed the loss of the electrochemical gradient across the inner membrane, uncoupling of oxidative phosphorylation, and colloid-osmotic swelling of mitochondria, events that result in the onset of cellular necrosis and may also be central to the apoptotic process [ 38 , 39 , 40 ], which could explain some of our previously obtained results [ 9 , 41 ]. From another perspective, this potential dissipation could also depend on chloride channels (CLIC) located in the mitochondrial membrane, the expression of which is regulated by apoptotic factors [ 42 , 43 ]. The CLIC overexpression results in the induction of several apoptotic events [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers

et al. 2022

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Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5−/− mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5−/− mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.

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“…CLIC proteins have been identified in multiple cellular compartments, including the nucleus, cytoplasm, mitochondria, and plasma membrane (Argenzio & Moolenaar, 2016 ; Jiang et al., 2014 ; Rao et al., 2018 ), making it unlikely that a single function underlies all CLIC‐related pathologies. Recombinant CLIC1, CLIC3, and CLIC4 have oxidoreductase enzymatic activity (Al Khamici et al., 2015 ; Hernandez‐Fernaud et al., 2017 ), suggesting they participate in cellular control of reactive oxygen (Al Khamici et al., 2022 ). While early studies implied that CLIC proteins demonstrate ion channel activity (Ashley, 2003 ), later reports have challenged this as a specific function (Argenzio & Moolenaar, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between tumour and stroma modifies CLIC4 cargo in extracellular vesicles

Sanchez,

Craig‐Lucas,

Cataisson

et al. 2023

J of Extracellular Bio

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Mouse models of breast cancer have revealed that tumour‐bearing hosts must express the oxidoreductase CLIC4 to develop lung metastases. In the absence of host CLIC4, primary tumours grow but the lung premetastatic niche is defective for metastatic seeding. Primary breast cancer cells release EVs that incorporate CLIC4 as cargo and circulate in plasma of wildtype tumour‐bearing hosts. CLIC4‐deficient breast cancer cells also form tumours in wildtype hosts and release EVs in plasma, but these EVs lack CLIC4, suggesting that the tumour is the source of the plasma‐derived EVs that carry CLIC4 as cargo. Paradoxically, circulating EVs are also devoid of CLIC4 when CLIC4‐expressing primary tumours are grown in CLIC4 knockout hosts. Thus, the incorporation of CLIC4 (and perhaps other factors) as EV cargo released from tumours involve specific signals from the surrounding stroma determined by its genetic composition. Since CLIC4 is also detected in circulating EVs from human breast cancer patients, future studies will address its association with disease.

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The oxidoreductase CLIC4 is required to maintain mitochondrial function and resistance to exogenous oxidants in breast cancer cells

Cited by 3 publications

References 81 publications

Chloride intracellular channel gene knockdown induces insect cell lines death and level increases of intracellular calcium ions

Chloride intracellular channel gene knockdown induces insect cell lines death and level increases of intracellular calcium ions

Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers

Crosstalk between tumour and stroma modifies CLIC4 cargo in extracellular vesicles

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