FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3127667298> ?p ?o ?g. }

• W3127667298 abstract "Cancer cells have increased energy requirements due to their enhanced proliferation activity. This energy demand is, among others, met by mitochondrial ATP production. Since the second messenger Ca 2+ maintains the activity of Krebs cycle dehydrogenases that fuel mitochondrial respiration, proper mitochondrial Ca 2+ uptake is crucial for a cancer cell survival. However, a mitochondrial Ca 2+ overload induces mitochondrial dysfunction and, ultimately, apoptotic cell death. Because of the vital importance of balancing mitochondrial Ca 2+ levels, a highly sophisticated machinery of multiple proteins manages mitochondrial Ca 2+ homeostasis. Notably, mitochondria sequester Ca 2+ preferentially at the interaction sites between mitochondria and the endoplasmic reticulum (ER), the largest internal Ca 2+ store, thus, pointing to mitochondrial-associated membranes (MAMs) as crucial hubs between cancer prosperity and cell death. To investigate potential regulatory mechanisms of the mitochondrial Ca 2+ uptake routes in cancer cells, we modulated mitochondria–ER tethering and the expression of UCP2 and analyzed mitochondrial Ca 2+ homeostasis under the various conditions. Hence, the expression of contributors to mitochondrial Ca 2+ regulation machinery was quantified by qRT-PCR. We further used data from The Cancer Genome Atlas (TCGA) to correlate these in vitro findings with expression patterns in human breast invasive cancer and human prostate adenocarcinoma. ER-mitochondrial linkage was found to support a mitochondrial Ca 2+ uptake route dependent on uncoupling protein 2 (UCP2) in cancer cells. Notably, combined overexpression of Rab32, a protein kinase A-anchoring protein fostering the ER-mitochondrial tethering, and UCP2 caused a significant drop in cancer cells' viability. Artificially enhanced ER-mitochondrial tethering further initiated a sudden decline in the expression of UCP2, probably as an adaptive response to avoid mitochondrial Ca 2+ overload. Besides, TCGA analysis revealed an inverse expression correlation between proteins stabilizing mitochondrial-ER linkage and UCP2 in tissues of human breast invasive cancer and prostate adenocarcinoma. Based on these results, we assume that cancer cells successfully manage mitochondrial Ca 2+ uptake to stimulate Ca 2+ -dependent mitochondrial metabolism while avoiding Ca 2+ -triggered cell death by fine-tuning ER-mitochondrial tethering and the expression of UCP2 in an inversed manner. Disruption of this equilibrium yields cancer cell death and may serve as a treatment strategy to specifically kill cancer cells." @default.
• W3127667298 created "2021-02-15" @default.
• W3127667298 creator A5039142110 @default.
• W3127667298 creator A5053111848 @default.
• W3127667298 creator A5065993592 @default.
• W3127667298 creator A5069588026 @default.
• W3127667298 creator A5078083544 @default.
• W3127667298 date "2021-02-04" @default.
• W3127667298 modified "2023-10-14" @default.
• W3127667298 title "Dynamic Control of Mitochondrial Ca2+ Levels as a Survival Strategy of Cancer Cells" @default.
• W3127667298 cites W1924192884 @default.
• W3127667298 cites W1951756999 @default.
• W3127667298 cites W1967184808 @default.
• W3127667298 cites W1970610775 @default.
• W3127667298 cites W1981049765 @default.
• W3127667298 cites W1983877797 @default.
• W3127667298 cites W1992887404 @default.
• W3127667298 cites W1997187136 @default.
• W3127667298 cites W1999911038 @default.
• W3127667298 cites W2002425246 @default.
• W3127667298 cites W2002439304 @default.
• W3127667298 cites W2002791298 @default.
• W3127667298 cites W2009657046 @default.
• W3127667298 cites W2019961716 @default.
• W3127667298 cites W2021810546 @default.
• W3127667298 cites W2023283007 @default.
• W3127667298 cites W2028533061 @default.
• W3127667298 cites W2035968737 @default.
• W3127667298 cites W2039848901 @default.
• W3127667298 cites W2052227340 @default.
• W3127667298 cites W2056145463 @default.
• W3127667298 cites W2059320820 @default.
• W3127667298 cites W2074607512 @default.
• W3127667298 cites W2078179312 @default.
• W3127667298 cites W2080678485 @default.
• W3127667298 cites W2093931854 @default.
• W3127667298 cites W2094094332 @default.
• W3127667298 cites W2105541649 @default.
• W3127667298 cites W2112384117 @default.
• W3127667298 cites W2121330845 @default.
• W3127667298 cites W2123869711 @default.
• W3127667298 cites W2139625864 @default.
• W3127667298 cites W2144171388 @default.
• W3127667298 cites W2148185042 @default.
• W3127667298 cites W2165750966 @default.
• W3127667298 cites W2165811472 @default.
• W3127667298 cites W2190226369 @default.
• W3127667298 cites W2291641483 @default.
• W3127667298 cites W2337436076 @default.
• W3127667298 cites W2363363069 @default.
• W3127667298 cites W2517397699 @default.
• W3127667298 cites W2521525326 @default.
• W3127667298 cites W2527503499 @default.
• W3127667298 cites W2552354243 @default.
• W3127667298 cites W2570732803 @default.
• W3127667298 cites W2594111041 @default.
• W3127667298 cites W2750285288 @default.
• W3127667298 cites W2763705386 @default.
• W3127667298 cites W2790222074 @default.
• W3127667298 cites W2793590421 @default.
• W3127667298 cites W2794056990 @default.
• W3127667298 cites W2805703034 @default.
• W3127667298 cites W2806153555 @default.
• W3127667298 cites W2900141042 @default.
• W3127667298 cites W2900151176 @default.
• W3127667298 cites W2903416169 @default.
• W3127667298 cites W2909858565 @default.
• W3127667298 cites W2916593356 @default.
• W3127667298 cites W2971815476 @default.
• W3127667298 cites W2982439704 @default.
• W3127667298 cites W3006611984 @default.
• W3127667298 cites W3009631343 @default.
• W3127667298 cites W3016481540 @default.
• W3127667298 cites W3022394898 @default.
• W3127667298 cites W3085056329 @default.
• W3127667298 cites W3085113313 @default.
• W3127667298 cites W3090051034 @default.
• W3127667298 cites W3091268995 @default.
• W3127667298 cites W386272597 @default.
• W3127667298 cites W4232939893 @default.
• W3127667298 doi "https://doi.org/10.3389/fcell.2021.614668" @default.
• W3127667298 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7889948" @default.
• W3127667298 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33614647" @default.
• W3127667298 hasPublicationYear "2021" @default.
• W3127667298 type Work @default.
• W3127667298 sameAs 3127667298 @default.
• W3127667298 citedByCount "18" @default.
• W3127667298 countsByYear W31276672982021 @default.
• W3127667298 countsByYear W31276672982022 @default.
• W3127667298 countsByYear W31276672982023 @default.
• W3127667298 crossrefType "journal-article" @default.
• W3127667298 hasAuthorship W3127667298A5039142110 @default.
• W3127667298 hasAuthorship W3127667298A5053111848 @default.
• W3127667298 hasAuthorship W3127667298A5065993592 @default.
• W3127667298 hasAuthorship W3127667298A5069588026 @default.
• W3127667298 hasAuthorship W3127667298A5078083544 @default.
• W3127667298 hasBestOaLocation W31276672981 @default.
• W3127667298 hasConcept C104317684 @default.
• W3127667298 hasConcept C111491248 @default.
• W3127667298 hasConcept C121608353 @default.

• next