VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases

Shoshan‐Barmatz, Varda; Shteinfer‐Kuzmine, Anna; Verma, Ankit

doi:10.3390/biom10111485

Cited by 126 publications

(126 citation statements)

References 352 publications

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“…It has been reported that the VDAC1 possesses Ca 2+ -binding sites, and its closure promotes Ca 2+ influx into mitochondria, which causes the opening of the mitochondrial permeability transition pore. Consequently, closure of the VDAC1 is recognised as a pro-apoptotic signal [ 25 ]. At the physiological state, [Ca 2+ ] in the mitochondrial intermembrane space is indistinguishable from that in the cytoplasm ([Ca 2+ ] c ) (around 100 nM) [ 26 ].…”

Section: Mitochondria-associated Membrane: a Platform For Er-mitochondria Ca 2+ Transportmentioning

confidence: 99%

A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

Zhang

Zhou

Crowley-McHattan

et al. 2021

IJERPH

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The physical contact site between a mitochondrion and endoplasmic reticulum (ER), named the mitochondria-associated membrane (MAM), has emerged as a fundamental platform for regulating the functions of the two organelles and several cellular processes. This includes Ca2+ transport from the ER to mitochondria, mitochondrial dynamics, autophagy, apoptosis signalling, ER stress signalling, redox reaction, and membrane structure maintenance. Consequently, the MAM is suggested to be involved in, and as a possible therapeutic target for, some common diseases and impairment in skeletal muscle function, such as insulin resistance and diabetes, obesity, neurodegenerative diseases, Duchenne muscular dystrophy, age-related muscle atrophy, and exercise-induced muscle damage. In the past decade, evidence suggests that alterations in Ca2+ transport from the ER to mitochondria, mediated by the macromolecular complex formed by IP3R, Grp75, and VDAC1, may be a universal mechanism for how ER-mitochondria cross-talk is involved in different physiological/pathological conditions mentioned above. A better understanding of the ER (or sarcoplasmic reticulum in muscle)-mitochondria Ca2+ transport system may provide a new perspective for exploring the mechanism of how the MAM is involved in the pathology of diseases and skeletal muscle dysfunction. This review provides a summary of recent research findings in this area.

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Section: Mitochondria-associated Membrane: a Platform For Er-mitochondria Ca 2+ Transportmentioning

confidence: 99%

A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

Zhang

Zhou

Crowley-McHattan

et al. 2021

IJERPH

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“…Some phenolic compounds cause cell death by targeting mitochondria [ 4 , 10 , 17 ]. We took the advantage of the intrinsic fluorescence of curcumin ( Figure 2 a) to monitor its uptake and subsequent subcellular localization [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…VDAC is unique porin, functionally present and abundant in the outer mitochondrial membrane. It acts as the mitochondrial gatekeeper, mediating ionic and metabolic fluxes between the cytosol and the mitochondrial intermembrane space [ 15 , 16 , 17 ]. The selectivity of this exchange critically depends on the conformational state of VDAC.…”

Section: Introductionmentioning

confidence: 99%

Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells

Olivas-Aguirre

Torres-López

Pottosin

et al. 2020

IJMS

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Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆Ψm) and [Ca2+]m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry. Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆Ψm and induced a significant [Ca2+]m increase, whereas inefficient phenols did not. Dissipation of the ∆Ψm by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca2+ uniporter, respectively. Ru360 prevented the phenol-induced [Ca2+]m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆Ψm depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death. Thus, all three phenols exert their antileukemic activity via mitochondrial Ca2+ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.

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“…Most current cancer chemotherapeutics cause cell death via apoptosis through two main apoptotic pathways: the extrinsic or death receptor pathway, and the intrinsic or mitochondrial pathway [ 1 , 2 ]. It is known that the mitochondrial apoptotic pathway is triggered by the opening of a large protein complex known as mPTP, although there is still much debate about mPTP components [ 5 , 39 , 40 , 41 , 42 ]. The human AACs [ 3 , 4 ] are among the most studied mPTP components/effectors and play a key role in regulating mPTP opening and thus in triggering the mitochondrial apoptotic pathway [ 5 , 6 , 7 , 39 , 40 , 41 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of ADP/ATP Carriers as a Biomarker of Metabolic Remodeling and Survival in Kidney Cancers

et al. 2020

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ADP/ATP carriers (AACs) are mitochondrial transport proteins playing a strategic role in maintaining the respiratory chain activity, fueling the cell with ATP, and also regulating mitochondrial apoptosis. To understand if AACs might represent a new molecular target for cancer treatment, we evaluated AAC expression levels in cancer/normal tissue pairs available on the Tissue Cancer Genome Atlas database (TCGA), observing that AACs are dysregulated in most of the available samples. It was observed that at least two AACs showed a significant differential expression in all the available kidney cancer/normal tissue pairs. Thus, we investigated AAC expression in the corresponding kidney non-cancer (HK2)/cancer (RCC-Shaw and CaKi-1) cell lines, grown in complete medium or serum starvation, for investigating how metabolic alteration induced by different growth conditions might influence AAC expression and resistance to mitochondrial apoptosis initiators, such as “staurosporine” or the AAC highly selective inhibitor “carboxyatractyloside”. Our analyses showed that AAC2 and AAC3 transcripts are more expressed than AAC1 in all the investigated kidney cell lines grown in complete medium, whereas serum starvation causes an increase of at least two AAC transcripts in kidney cancer cell lines compared to non-cancer cells. However, the total AAC protein content is decreased in the investigated cancer cell lines, above all in the serum-free medium. The observed decrease in AAC protein content might be responsible for the decrease of OXPHOS activity and for the observed lowered sensitivity to mitochondrial apoptosis induced by staurosporine or carboxyatractyloside. Notably, the cumulative probability of the survival of kidney cancer patients seriously decreases with the decrease of AAC1 expression in KIRC and KIRP tissues making AAC1 a possible new biomarker of metabolic remodeling and survival in kidney cancers.

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VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases

Cited by 126 publications

References 352 publications

A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells

Differential Expression of ADP/ATP Carriers as a Biomarker of Metabolic Remodeling and Survival in Kidney Cancers

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