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000284337 1001_ $$aVetralla, Massimo$$b0
000284337 245__ $$aTMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis.
000284337 260__ $$a[London]$$bSpringer Nature$$c2025
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000284337 520__ $$aThe bidirectional transport of Ca2+ into and out of mitochondria regulates metabolism, signaling, and cell fate. While influx is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, efflux mechanisms are more diversified, involving Na⁺ or H⁺ exchange pathways. We here demonstrate that TMEM65 is a fundamental component of the Ca2+ efflux machinery of mitochondria. Its overexpression specifically enhances Na⁺- and Li⁺-dependent mitochondrial Ca²⁺ extrusion. This effect is inhibited by CGP-37157 and does not depends on NCLX, currently considered the bona fide mitochondrial Na+/Ca2+ exchanger. Its downregulation chronically elevates basal [Ca²⁺]mt and impairs efflux upon stimulation. In Caenorhabditis elegans, deletion of TMEM65 homologs compromises embryonic development under mild thermal stress, causing necrotic lesions that are suppressed by genetic inhibition of MCU-1. These findings highlight a molecular component that may be relevant in pathological settings in which excessive mitochondrial Ca2+ accumulation critically contribute to degenerative pathways.
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000284337 650_7 $$0SY7Q814VUP$$2NLM Chemicals$$aCalcium
000284337 650_7 $$2NLM Chemicals$$aCaenorhabditis elegans Proteins
000284337 650_7 $$2NLM Chemicals$$aMembrane Proteins
000284337 650_7 $$2NLM Chemicals$$aCalcium Channels
000284337 650_7 $$05PE9FDE8GB$$2NLM Chemicals$$aClonazepam
000284337 650_7 $$2NLM Chemicals$$amitochondrial calcium uniporter
000284337 650_7 $$2NLM Chemicals$$aSodium-Calcium Exchanger
000284337 650_7 $$075450-34-9$$2NLM Chemicals$$aCGP 37157
000284337 650_7 $$2NLM Chemicals$$aMitochondrial Proteins
000284337 650_7 $$2NLM Chemicals$$aThiazepines
000284337 650_2 $$2MeSH$$aAnimals
000284337 650_2 $$2MeSH$$aMitochondria: metabolism
000284337 650_2 $$2MeSH$$aCaenorhabditis elegans: metabolism
000284337 650_2 $$2MeSH$$aCaenorhabditis elegans: genetics
000284337 650_2 $$2MeSH$$aCalcium: metabolism
000284337 650_2 $$2MeSH$$aHomeostasis
000284337 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: metabolism
000284337 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: genetics
000284337 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000284337 650_2 $$2MeSH$$aMembrane Proteins: genetics
000284337 650_2 $$2MeSH$$aCalcium Channels: metabolism
000284337 650_2 $$2MeSH$$aCalcium Channels: genetics
000284337 650_2 $$2MeSH$$aClonazepam: analogs & derivatives
000284337 650_2 $$2MeSH$$aClonazepam: pharmacology
000284337 650_2 $$2MeSH$$aSodium-Calcium Exchanger: metabolism
000284337 650_2 $$2MeSH$$aSodium-Calcium Exchanger: genetics
000284337 650_2 $$2MeSH$$aHumans
000284337 650_2 $$2MeSH$$aMitochondrial Proteins: metabolism
000284337 650_2 $$2MeSH$$aMitochondrial Proteins: genetics
000284337 650_2 $$2MeSH$$aThiazepines
000284337 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b1$$eFirst author$$udzne
000284337 7001_ $$aKahsay, Asrat$$b2
000284337 7001_ $$aCadenelli, Vanessa$$b3
000284337 7001_ $$0P:(DE-2719)2812562$$aScifo, Enzo$$b4$$udzne
000284337 7001_ $$0P:(DE-2719)9001936$$aXie, Beijia$$b5$$udzne
000284337 7001_ $$aSbrissa, Miriana$$b6
000284337 7001_ $$0P:(DE-2719)9002913$$aHabert, Maelle$$b7$$udzne
000284337 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b8
000284337 7001_ $$00000-0001-7044-5097$$aRizzuto, Rosario$$b9
000284337 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b10
000284337 7001_ $$00000-0003-3796-8907$$aDe Stefani, Diego$$b11
000284337 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-67647-y$$gVol. 17, no. 1, p. 923$$n1$$p923$$tNature Communications$$v17$$x2041-1723$$y2025
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