000095546 001__ 95546
000095546 005__ 20231116120808.0
000095546 0247_ $$2doi$$a10.1126/sciadv.aba5345
000095546 0248_ $$2sideral$$a119601
000095546 037__ $$aART-2020-119601
000095546 041__ $$aeng
000095546 100__ $$aLechuga-Vieco, A.V.
000095546 245__ $$aCell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics
000095546 260__ $$c2020
000095546 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095546 5203_ $$aHeteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues.
000095546 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/SAF2017-84494-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-79126-R$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2016-78114-R$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2015-65633-R$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 805046-EvoConBiO$$9info:eu-repo/grantAgreement/EC/H2020/805046/EU/Uncovering and engineering the principles governing evolution and cellular control of bioenergetic organelles /EvoConBiO$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 666918-BatCure$$9info:eu-repo/grantAgreement/EC/H2020/666918/EU/Developing new therapies for Batten disease /BatCure$$9info:eu-repo/grantAgreement/ES/AEI/MDM-2017-0720$$9info:eu-repo/grantAgreement/ES/MINECO/SEV-2015-0505
000095546 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000095546 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095546 700__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, A.
000095546 700__ $$aJohnston, I.G.
000095546 700__ $$aProta, G.
000095546 700__ $$aGileadi, U.
000095546 700__ $$aJusto-Méndez, R.
000095546 700__ $$aAcín-Pérez, R.
000095546 700__ $$aMartínez-de-Mena, R.
000095546 700__ $$aFernández-Toro, J.M.
000095546 700__ $$aJimenez-Blasco, D.
000095546 700__ $$aMora, A.
000095546 700__ $$aNicolás-Ávila, J.A.
000095546 700__ $$aSantiago, D.J.
000095546 700__ $$aPriori, S.G.
000095546 700__ $$aBolaños, J.P.
000095546 700__ $$aSabio, G.
000095546 700__ $$aCriado, L.M.
000095546 700__ $$aRuíz-Cabello, J.
000095546 700__ $$aCerundolo, V.
000095546 700__ $$aJones, N.S.
000095546 700__ $$aEnríquez, J.A.
000095546 773__ $$g6, 31 (2020), eaba5345 [13 pp.]$$pSci. adv.$$tScience advances$$x2375-2548
000095546 8564_ $$s1194047$$uhttps://zaguan.unizar.es/record/95546/files/texto_completo.pdf$$yVersión publicada
000095546 8564_ $$s22908$$uhttps://zaguan.unizar.es/record/95546/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095546 909CO $$ooai:zaguan.unizar.es:95546$$particulos$$pdriver
000095546 951__ $$a2023-11-16-12:00:39
000095546 980__ $$aARTICLE