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| 037 | _ | _ | |a DZNE-2026-00112 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Vetralla, Massimo |b 0 |
| 245 | _ | _ | |a TMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis. |
| 260 | _ | _ | |a [London] |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1769431581_1864 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The bidirectional transport of Ca2+ into and out of mitochondria regulates metabolism, signaling, and cell fate. While influx is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, efflux mechanisms are more diversified, involving Na⁺ or H⁺ exchange pathways. We here demonstrate that TMEM65 is a fundamental component of the Ca2+ efflux machinery of mitochondria. Its overexpression specifically enhances Na⁺- and Li⁺-dependent mitochondrial Ca²⁺ extrusion. This effect is inhibited by CGP-37157 and does not depends on NCLX, currently considered the bona fide mitochondrial Na+/Ca2+ exchanger. Its downregulation chronically elevates basal [Ca²⁺]mt and impairs efflux upon stimulation. In Caenorhabditis elegans, deletion of TMEM65 homologs compromises embryonic development under mild thermal stress, causing necrotic lesions that are suppressed by genetic inhibition of MCU-1. These findings highlight a molecular component that may be relevant in pathological settings in which excessive mitochondrial Ca2+ accumulation critically contribute to degenerative pathways. |
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| 650 | _ | 7 | |a Calcium |0 SY7Q814VUP |2 NLM Chemicals |
| 650 | _ | 7 | |a Caenorhabditis elegans Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Membrane Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Calcium Channels |2 NLM Chemicals |
| 650 | _ | 7 | |a Clonazepam |0 5PE9FDE8GB |2 NLM Chemicals |
| 650 | _ | 7 | |a mitochondrial calcium uniporter |2 NLM Chemicals |
| 650 | _ | 7 | |a Sodium-Calcium Exchanger |2 NLM Chemicals |
| 650 | _ | 7 | |a CGP 37157 |0 75450-34-9 |2 NLM Chemicals |
| 650 | _ | 7 | |a Mitochondrial Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Thiazepines |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Mitochondria: metabolism |2 MeSH |
| 650 | _ | 2 | |a Caenorhabditis elegans: metabolism |2 MeSH |
| 650 | _ | 2 | |a Caenorhabditis elegans: genetics |2 MeSH |
| 650 | _ | 2 | |a Calcium: metabolism |2 MeSH |
| 650 | _ | 2 | |a Homeostasis |2 MeSH |
| 650 | _ | 2 | |a Caenorhabditis elegans Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Caenorhabditis elegans Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Membrane Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Membrane Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Calcium Channels: metabolism |2 MeSH |
| 650 | _ | 2 | |a Calcium Channels: genetics |2 MeSH |
| 650 | _ | 2 | |a Clonazepam: analogs & derivatives |2 MeSH |
| 650 | _ | 2 | |a Clonazepam: pharmacology |2 MeSH |
| 650 | _ | 2 | |a Sodium-Calcium Exchanger: metabolism |2 MeSH |
| 650 | _ | 2 | |a Sodium-Calcium Exchanger: genetics |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mitochondrial Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mitochondrial Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Thiazepines |2 MeSH |
| 700 | 1 | _ | |a Wischhof, Lena |0 P:(DE-2719)2811527 |b 1 |e First author |u dzne |
| 700 | 1 | _ | |a Kahsay, Asrat |b 2 |
| 700 | 1 | _ | |a Cadenelli, Vanessa |b 3 |
| 700 | 1 | _ | |a Scifo, Enzo |0 P:(DE-2719)2812562 |b 4 |u dzne |
| 700 | 1 | _ | |a Xie, Beijia |0 P:(DE-2719)9001936 |b 5 |u dzne |
| 700 | 1 | _ | |a Sbrissa, Miriana |b 6 |
| 700 | 1 | _ | |a Habert, Maelle |0 P:(DE-2719)9002913 |b 7 |u dzne |
| 700 | 1 | _ | |a Ehninger, Dan |0 P:(DE-2719)2289209 |b 8 |
| 700 | 1 | _ | |a Rizzuto, Rosario |0 0000-0001-7044-5097 |b 9 |
| 700 | 1 | _ | |a Bano, Daniele |0 P:(DE-2719)2158358 |b 10 |
| 700 | 1 | _ | |a De Stefani, Diego |0 0000-0003-3796-8907 |b 11 |
| 773 | _ | _ | |a 10.1038/s41467-025-67647-y |g Vol. 17, no. 1, p. 923 |0 PERI:(DE-600)2553671-0 |n 1 |p 923 |t Nature Communications |v 17 |y 2025 |x 2041-1723 |
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