<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Roussos, Antonis</style></author><author><style face="normal" font="default" size="100%">Kitopoulou, Katerina</style></author><author><style face="normal" font="default" size="100%">Fivos Borbolis</style></author><author><style face="normal" font="default" size="100%">Ploumi, Christina</style></author><author><style face="normal" font="default" size="100%">Gianniou, Despoina D.</style></author><author><style face="normal" font="default" size="100%">Li, Zhiquan</style></author><author><style face="normal" font="default" size="100%">He, Haijun</style></author><author><style face="normal" font="default" size="100%">Tsakiri, Eleni</style></author><author><style face="normal" font="default" size="100%">Borland, Helena</style></author><author><style face="normal" font="default" size="100%">Kostakis, Ioannis K.</style></author><author><style face="normal" font="default" size="100%">Samiotaki, Martina</style></author><author><style face="normal" font="default" size="100%">Trougakos, Ioannis P.</style></author><author><style face="normal" font="default" size="100%">Bohr, Vilhelm A</style></author><author><style face="normal" font="default" size="100%">Palikaras, Konstantinos</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing</style></title><secondary-title><style face="normal" font="default" size="100%">Autophagy</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">calcium</style></keyword><keyword><style  face="normal" font="default" size="100%">cellular senescence</style></keyword><keyword><style  face="normal" font="default" size="100%">ER</style></keyword><keyword><style  face="normal" font="default" size="100%">geroprotection</style></keyword><keyword><style  face="normal" font="default" size="100%">Lysosome</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondria</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2025</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1080/15548627.2025.2561073https://www.ncbi.nlm.nih.gov/pubmed/40944367</style></url></web-urls></urls><pub-location><style face="normal" font="default" size="100%">United States</style></pub-location><pages><style face="normal" font="default" size="100%">1-26</style></pages><isbn><style face="normal" font="default" size="100%">1554-8635</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Mitochondrial dysfunction and impaired mitophagy are hallmarks of ageing and age-related pathologies. Disrupted inter-organellar communication among mitochondria, endoplasmic reticulum (ER), and lysosomes, further contributes to cellular dysfunction. While mitophagy has emerged as a promising target for neuroprotection and geroprotection, its potential to restore age-associated defects in organellar crosstalk remains unclear. Here, we show that mitophagy deficiency deregulates the morphology and homeostasis of mitochondria, ER and lysosomes, mirroring age-related alterations. In contrast, Urolithin A (UA), a gut-derived metabolite and potent mitophagy inducer, restores inter-organellar communication via calcium signaling, thereby, promoting mitophagy, healthspan and longevity. Our multi-omic analysis reveals that UA reorganizes ER, mitochondrial and lysosomal networks, linking inter-organellar dynamics to mitochondrial quality control. In Caenorhabditis elegans, UA induces calcium release from the ER, enhances lysosomal activity, and drives DRP-1/DNM1L/DRP1-mediated mitochondrial fission, culminating in efficient mitophagy. Calcium chelation abolishes UA-induced mitophagy, blocking its beneficial impact on muscle function and lifespan, underscoring the critical role of calcium signaling in UA's geroprotective effects. Furthermore, UA-induced calcium elevation activates mitochondrial biogenesis via UNC-43/CAMK2D and SKN-1/NFE2L2/Nrf2 pathways, which are both essential for healthspan and lifespan extension. Similarly, in mammalian cells, UA increases intracellular calcium, enhances mitophagy and mitochondrial metabolism, and mitigates stress-induced senescence in a calcium-dependent manner. Our findings uncover a conserved mechanism by which UA-induced mitophagy restores inter-organellar communication, supporting cellular homeostasis and organismal health.Abbreviations: Ca(2+): calcium ions; BJ: human foreskin fibroblasts; BNIP3: BCL2 interacting protein 3; BP: bipyridyl; CAMK2D: calcium/calmodulin dependent protein kinase II delta; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DEGs: differentially expressed genes; DEPs : differentially expressed peptides; DFP: deferiprone; DNM1L/DRP1: dynamin 1 like; EGTA: ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid; EMC: endoplasmic reticulum membrane protein complex; ER: endoplasmic reticulum; FCCP: carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone; GO: gene ontology; GSVA: Gene Set Variation Analysis; HUVECs: human umbilical vein endothelial cells; IMM: inner mitochondrial membrane; ITPR/InsP3R: inositol 1,4,5-triphosphate receptor; MAM: mitochondria-associated ER membrane; MAPK: mitogen-activated protein kinase; MCU: mitochondrial calcium uniporter; MEFs: mouse embryonic fibroblasts; NAC : N-acetylcysteine; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NMN: nicotinamide mononucleotide; NR: nicotinamide riboside; OMM: outer mitochondrial membrane; PCA: principal-component analysis; PPARGC1A/PGC1α: PPARG coactivator 1 alpha; PQ: paraquat; TMCO: transmembrane and coiled-coil domains 1; TMRE: tetramethylrhodamine ethyl ester perchlorate; UA: urolithin A; VDAC: voltage dependent anion channel.</style></abstract></record></records></xml>