1. Home

ISITE - Sénescence et transfert mitochondrial dans les cellules stromales mésenchymateuses : rôle de la mitofusine 1 dans la communication avec les cellules immunitaires et tumorales

Offre de thèse

ISITE - Sénescence et transfert mitochondrial dans les cellules stromales mésenchymateuses : rôle de la mitofusine 1 dans la communication avec les cellules immunitaires et tumorales

Date limite de candidature

07-08-2026

Date de début de contrat

01-10-2026

Directeur de thèse

DE ISLA Natalia

Encadrement

This thesis is part of a France/Uruguay cooperation program funded by the ECOS-Sud program. It will be hosted at the IMoPA laboratory (CNRS UMR 7365, University of Lorraine, Nancy, France) and co-directed by Dr. Celia Quijano, Professor of Biochemistry and Metabolism at Universidad de la República (Uruguay), a specialist in senescence, mitochondrial biology, and cellular metabolism, and co-supervised by Dr. Jessica Schiavi-Tritz, an expert in the purification and characterization of extracellular vesicles, and Dr. Guillermo Barreto, a specialist in epigenetics.SCHI

Type de contrat

Concours pour un contrat doctoral

Candidater à cette offre

école doctorale

BioSE - Biologie Santé Environnement

équipe

Equipe 6 : Cell-engineering and Immunomodulation of Inflammatoryand Neoplastic Disorders (CImIND

contexte

Senescent cells acquire a secretory phenotype (SASP) that remodels their microenvironment and can promote chronic inflammation, immune dysfunction, and tumor progression. MSCs, key regulators of the hematopoietic niche, undergo profound senescence-associated remodeling in leukemia and transplantation settings. Recent evidence shows that MSCs transfer mitochondria to immune and tumor cells, reprogramming their metabolism, yet the molecular mechanisms controlling this transfer remain poorly understood. Mitofusin 1, a central regulator of mitochondrial dynamics, is a promising candidate linking senescence, mitochondrial trafficking, and intercellular communication.

spécialité

Sciences de la Vie et de la Santé - BioSE

laboratoire

IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire

Mots clés

cellules stromales mésenchymateuses, Sénescence, mitofusine 1, transfert mitochondrial

Détail de l'offre

La sénescence cellulaire, caractérisée par un arrêt stable du cycle cellulaire et un phénotype sécrétoire associé (SASP), joue un rôle ambivalent dans le cancer et les maladies hématologiques, agissant à la fois comme mécanisme suppresseur de tumeur et comme moteur d'un microenvironnement pro-inflammatoire favorisant la progression tumorale. Les cellules stromales mésenchymateuses (CSM) dérivées de la moelle osseuse, régulateurs clés de la niche hématopoïétique, subissent un remodelage fonctionnel majeur au cours de la sénescence, notamment dans des contextes pathologiques tels que la leucémie et la greffe de cellules souches hématopoïétiques. Des études récentes ont montré que ces cellules sont capables de transférer des mitochondries aux cellules immunitaires et tumorales avoisinantes, reprogrammant ainsi leur métabolisme et leur fonction. Ce projet vise à étudier le rôle de la mitofusine 1 (MFN1), régulateur clé de la dynamique mitochondriale, dans le contrôle de ce transfert et ses conséquences métaboliques, épigénétiques et immunitaires sur les cellules receveuses. La stratégie expérimentale s'articule autour de trois axes de travail complémentaires : (1) la caractérisation des altérations métaboliques et mitochondriales associées à la sénescence dans les CSM, (2) l'analyse mécanistique du rôle de MFN1 dans le transfert mitochondrial intercellulaire, et (3) l'étude de la reprogrammation épigénétique et fonctionnelle des cellules immunitaires receveuses. S'appuyant sur une collaboration France/Uruguay (Nancy/Montevideo) associant des expertises en biologie de la sénescence, biologie mitochondriale et épigénétique, ce projet vise à identifier de nouvelles cibles thérapeutiques pour les maladies hématologiques.

Keywords

Mesenchymal stromal cells, Senescence, mitofusin 1, mitochondrial transfer

Subject details

Cellular senescence, characterized by a stable cell cycle arrest and an associated secretory phenotype (SASP), plays an ambivalent role in cancer and hematological diseases, acting both as a tumor-suppressive mechanism and as a driver of a pro-inflammatory microenvironment that fosters tumor progression. Bone marrow–derived mesenchymal stromal cells (MSCs), key regulators of the hematopoietic niche, undergo major functional remodeling during senescence, particularly in pathological contexts such as leukemia and hematopoietic stem cell transplantation. Recent studies have shown that these cells can transfer mitochondria to neighboring immune and tumor cells, thereby reprogramming their metabolism and function. This project aims to investigate the role of mitofusin 1 (MFN1), a key regulator of mitochondrial dynamics, in controlling this transfer and its metabolic, epigenetic, and immune consequences on recipient cells. The experimental strategy is organized around three complementary work packages: (1) characterization of senescence-associated metabolic and mitochondrial alterations in MSCs, (2) mechanistic analysis of the role of MFN1 in intercellular mitochondrial transfer, and (3) investigation of the epigenetic and functional reprogramming of recipient immune cells. Built on a France/Uruguay collaboration (Nancy/Montevideo) combining expertise in senescence biology, mitochondrial biology, and epigenetics, this project seeks to identify new therapeutic targets for hematological diseases.

Profil du candidat

Nous recherchons un(e) candidat(e) très motivé(e), disposant d'une solide formation en sciences de la vie, idéalement titulaire d'un master (ou équivalent) en biologie cellulaire, biologie moléculaire, immunologie, biochimie, ou dans un domaine connexe. Le/la candidat(e) devra posséder de solides connaissances en biologie cellulaire et moléculaire fondamentale, ainsi qu'un fort intérêt pour la biologie mitochondriale, le métabolisme cellulaire, la sénescence et/ou l'immunologie.
Une expérience préalable en culture cellulaire, dans les techniques de base de biologie moléculaire (PCR, Western blot, immunofluorescence) et en analyse de données est attendue. Une expérience dans un ou plusieurs des domaines suivants sera considérée comme un atout : fonction mitochondriale, cytométrie en flux, microscopie confocale, vésicules extracellulaires, ou approches omiques.
Au-delà des compétences techniques, le/la candidat(e) idéal(e) devra faire preuve d'une forte curiosité scientifique, d'autonomie, de rigueur et d'esprit critique. La capacité à travailler dans un environnement de recherche interdisciplinaire et international est essentielle, tout comme de bonnes compétences en communication et un bon niveau d'anglais scientifique (écrit et oral). Une forte motivation pour la recherche fondamentale et pour la mobilité internationale est requise.

Candidate profile

We are seeking a highly motivated candidate with a strong background in life sciences, ideally holding a Master's degree (or equivalent) in cell biology, molecular biology, immunology, biochemistry, or a related field. The candidate should have solid knowledge of fundamental cellular and molecular biology and a strong interest in mitochondrial biology, cellular metabolism, senescence, and/or immunology.
Previous experience in cell culture, basic molecular biology techniques (PCR, Western blot, immunofluorescence), and data analysis is expected. Experience in one or more of the following areas will be considered an asset: mitochondrial function, flow cytometry, confocal microscopy, extracellular vesicles, or omics approaches.
Beyond technical skills, the ideal candidate should demonstrate strong scientific curiosity, autonomy, rigor, and critical thinking. The ability to work in an interdisciplinary and international research environment is essential, as well as good communication skills and a good level of scientific English (written and spoken). A strong motivation for fundamental research and international mobility is required.

Référence biblio

• [L. Hayflick, The Limited in Vitro Lifetime of Human Diploid Cell Strains, Exp Cell Res 37 (1965) 614–36.
• [F. d'Adda di Fagagna, P.M. Reaper, L. Clay-Farrace, H. Fiegler, P. Carr, T. Von Zglinicki, G. Saretzki, N.P. Carter, S.P. Jackson, A DNA damage checkpoint response in telomere-initiated senescence, Nature 426 (2003) 194–8. https://doi.org/10.1038/nature02118.
• J. Martinez, D. Tarallo, L. Martinez-Palma, S. Victoria, M. Bresque, S. Rodriguez-Bottero, I. Marmisolle, C. Escande, P. Cassina, G. Casanova, M. Bollati-Fogolin, C. Agorio, M. Moreno, C. Quijano, Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells, The Biochemical Journal 476 (2019) 2463–2486. https://doi.org/10.1042/BCJ20190405.
• A. Calcinotto, J. Kohli, E. Zagato, L. Pellegrini, M. Demaria, A. Alimonti, Cellular Senescence: Aging, Cancer, and Injury, Physiological Reviews 99 (2019) 1047–1078. https://doi.org/10.1152/physrev.00020.2018.
• D. Munoz-Espin, M. Serrano, Cellular senescence: from physiology to pathology, Nature Reviews. Molecular Cell Biology 15 (2014) 482–96. https://doi.org/10.1038/nrm3823.
• P. Lecot, F. Alimirah, P.Y. Desprez, J. Campisi, C. Wiley, Context-dependent effects of cellular senescence in cancer development, British Journal of Cancer 114 (2016) 1180–4. https://doi.org/10.1038/bjc.2016.115.
• D.J. Baker, B.G. Childs, M. Durik, M.E. Wijers, C.J. Sieben, J. Zhong, R.A. Saltness, K.B. Jeganathan, G.C. Verzosa, A. Pezeshki, K. Khazaie, J.D. Miller, J.M. van Deursen, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature 530 (2016) 184–9. https://doi.org/10.1038/nature16932.
• [M. Demaria, M.N. O'Leary, J. Chang, L. Shao, S. Liu, F. Alimirah, K. Koenig, C. Le, N. Mitin, A.M. Deal, S. Alston, E.C. Academia, S. Kilmarx, A. Valdovinos, B. Wang, A. de Bruin, B.K. Kennedy, S. Melov, D. Zhou, N.E. Sharpless, H. Muss, J. Campisi, Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse, Cancer Discovery 7 (2017) 165–176. https://doi.org/10.1158/2159-8290.CD-16-0241.
• J.R. Dorr, Y. Yu, M. Milanovic, G. Beuster, C. Zasada, J.H. Dabritz, J. Lisec, D. Lenze, A. Gerhardt, K. Schleicher, S. Kratzat, B. Purfurst, S. Walenta, W. Mueller-Klieser, M. Graler, M. Hummel, U. Keller, A.K. Buck, B. Dorken, L. Willmitzer, M. Reimann, S. Kempa, S. Lee, C.A. Schmitt, Synthetic lethal metabolic targeting of cellular senescence in cancer therapy, Nature 501 (2013) 421–5. https://doi.org/10.1038/nature12437.
• C. Quijano, L. Cao, M.M. Fergusson, H. Romero, J. Liu, S. Gutkind, I. Rovira, R.P. Mohney, E.D. Karoly, T. Finkel, Oncogene-induced senescence results in marked metabolic and bioenergetic alterations, Cell Cycle 11 (2012) 1383–92. https://doi.org/10.4161/cc.19800.
• S. Takebayashi, H. Tanaka, S. Hino, Y. Nakatsu, T. Igata, A. Sakamoto, M. Narita, M. Nakao, Retinoblastoma protein promotes oxidative phosphorylation through upregulation of glycolytic genes in oncogene-induced senescent cells, Aging Cell 14 (2015) 689–97. https://doi.org/10.1111/acel.12351.
• C. Correia-Melo, F.D. Marques, R. Anderson, G. Hewitt, R. Hewitt, J. Cole, B.M. Carroll, S. Miwa, J. Birch, A. Merz, M.D. Rushton, M. Charles, D. Jurk, S.W. Tait, R. Czapiewski, L. Greaves, G. Nelson, Y.M. Bohlooly, S. Rodriguez-Cuenca, A. Vidal-Puig, D. Mann, G. Saretzki, G. Quarato, D.R. Green, P.D.
Adams, T. von Zglinicki, V.I. Korolchuk, J.F. Passos, Mitochondria are required for pro-ageing features of the senescent phenotype, The EMBO Journal 35 (2016) 724–42. https://doi.org/10.15252/embj.201592862.
• [M. Roy, P.H. Reddy, M. Iijima, H. Sesaki, Mitochondrial division and fusion in metabolism, Current Opinion in Cell Biology 33 (2015) 111–8. https://doi.org/10.1016/j.ceb.2015.02.001.
• P. Mishra, D.C. Chan, Metabolic regulation of mitochondrial dynamics, The Journal of Cell Biology 212 (2016) 379–87. https://doi.org/10.1083/jcb.201511036.
• [O.M. de Brito, L. Scorrano, Mitofusin 2 tethers endoplasmic reticulum to mitochondria, Nature 456 (2008) 605–10. https://doi.org/10.1038/nature07534.
• D. Tarallo, J. Martínez, A. Leyva, A. Mónaco, C. Perroni, M. Tassano, J.P. Gambini, M. Cappetta, R. Durán, M. Moreno, C. Quijano, Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy, Sci Rep 14 (2024) 909. https://doi.org/10.1038/s41598-024-51427-7.
• S. Victorelli, H. Salmonowicz, J. Chapman, H. Martini, M.G. Vizioli, J.S. Riley, C. Cloix, E. Hall-Younger, J. Machado Espindola-Netto, D. Jurk, A.B. Lagnado, L. Sales Gomez, J.N. Farr, D. Saul, R. Reed, G. Kelly, M. Eppard, L.C. Greaves, Z. Dou, N. Pirius, K. Szczepanowska, R.A. Porritt, H. Huang, T.Y. Huang, D.A. Mann, C.A. Masuda, S. Khosla, H. Dai, S.H. Kaufmann, E. Zacharioudakis, E. Gavathiotis, N.K. LeBrasseur, X. Lei, A.G. Sainz, V.I. Korolchuk, P.D. Adams, G.S. Shadel, S.W.G. Tait, J.F. Passos, Apoptotic stress causes mtDNA release during senescence and drives the SASP, Nature 622 (2023) 627–636. https://doi.org/10.1038/s41586-023-06621-4.
• S. Short, E. Fielder, S. Miwa, T. von Zglinicki, Senolytics and senostatics as adjuvant tumour therapy, EBioMedicine 41 (2019) 683–692. https://doi.org/10.1016/j.ebiom.2019.01.056.
• Y. Zhu, T. Tchkonia, T. Pirtskhalava, A.C. Gower, H. Ding, N. Giorgadze, A.K. Palmer, Y. Ikeno, G.B. Hubbard, M. Lenburg, S.P. O'Hara, N.F. LaRusso, J.D. Miller, C.M. Roos, G.C. Verzosa, N.K. LeBrasseur, J.D. Wren, J.N. Farr, S. Khosla, M.B. Stout, S.J. McGowan, H. Fuhrmann-Stroissnigg, A.U. Gurkar, J. Zhao, D. Colangelo, A. Dorronsoro, Y.Y. Ling, A.S. Barghouthy, D.C. Navarro, T. Sano, P.D. Robbins, L.J. Niedernhofer, J.L. Kirkland, The Achilles' heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell 14 (2015) 644–58. https://doi.org/10.1111/acel.12344.
• P. Mishra, D.C. Chan, Mitochondrial dynamics and inheritance during cell division, development and disease, Nat Rev Mol Cell Biol 15 (2014) 634–646. https://doi.org/10.1038/nrm3877.
• N. Borcherding, J.R. Brestoff, The power and potential of mitochondria transfer, Nature 623 (2023) 283–291. https://doi.org/10.1038/s41586-023-06537-z.
• C. Pochon, R. Perouf, A. Bertrand, A.-B. Notarantonio, N. Charif, M.D.C. Bittencourt, G. Fouquet, G. Cauchois, C. Voisin, D. Bensoussan, P. Emond, H. Sartelet, D. Moulin, N. De Isla, M. D'Aveni, M.-T. Rubio, Wharton's jelly mesenchymal stromal cells inhibit T-cell proliferation by synergistic IDO and mitochondrial transfer mechanisms, (2023). https://doi.org/10.21203/rs.3.rs-3655024/v1.
• R. Perouf, M. Hadid, A. Guelton, N. Charif, C. Pochon, M. D'Aveni, S. Pagliuca, M.-T. Rubio, N. De Isla, Senescence and Mitochondrial Transfer Ability of Bone Marrow Mesenchymal Stromal Cells Influence Patterns of Alloreactivity after Allogeneic Hematopoietic Stem Cell Transplantation, Blood 142 (2023) 1334–1334. https://doi.org/10.1182/blood-2023-189093.
• .V. Gorgoulis, P.D. Adams, A. Alimonti, D.C. Bennett, O. Bischof, C. Bishop, J. Campisi, M. Collado, K. Evangelou, G. Ferbeyre, J. Gil, E. Hara, V. Krizhanovsky, D. Jurk, A.B. Maier, M. Narita, L. Niedernhofer, J.F. Passos, P.D. Robbins, C.A. Schmitt, J. Sedivy, K. Vougas, T. Von Zglinicki, D. Zhou, M. Serrano, M. Demaria, Cellular Senescence: Defining a Path Forward, Cell 179 (2019) 813–827. https://doi.org/10.1016/j.cell.2019.10.005.
• [I. Marmisolle, J. Martinez, J. Liu, M. Mastrogiovanni, M.M. Fergusson, I. Rovira, L. Castro, A. Trostchansky, M. Moreno, L. Cao, T. Finkel, C. Quijano, Reciprocal regulation of acetyl-CoA carboxylase 1 and senescence in human fibroblasts involves oxidant mediated p38 MAPK activation, Archives of Biochemistry and Biophysics 613 (2017) 12–22. https://doi.org/10.1016/j.abb.2016.10.016.
• M.D. Brand, D.G. Nicholls, Assessing mitochondrial dysfunction in cells, Biochem J 435 (2011) 297–312. https://doi.org/10.1042/BJ20110162 BJ20110162 [pii].
• [S. Abounit, E. Delage, C. Zurzolo, Identification and Characterization of Tunneling Nanotubes for Intercellular Trafficking, CP Cell Biology 67 (2015). https://doi.org/10.1002/0471143030.cb1210s67.
• C. Quijano, M. Trujillo, L. Castro, A. Trostchansky, Interplay between oxidant species and energy metabolism, Redox Biol 8 (2016) 28–42. https://doi.org/10.1016/j.redox.2015.11.010.
• J. Martínez, I. Marmisolle, D. Tarallo, C. Quijano, Mitochondrial bioenergetics and dynamics in secretion processes, Frontiers in Endocrinology (2020). https://doi.org/10.3389/fendo.2020.00319.
• M. Garcia-Roche, A. Casal, M. Carriquiry, R. Radi, C. Quijano, A. Cassina, Respiratory analysis of coupled mitochondria in cryopreserved liver biopsies, Redox Biology 17 (2018) 207–212. https://doi.org/10.1016/j.redox.2018.03.008.
• M. Garcia-Roche, A. Casal, D.A. Mattiauda, M. Ceriani, A. Jasinsky, M. Mastrogiovanni, A. Trostchansky, M. Carriquiry, A. Cassina, C. Quijano, Impaired hepatic mitochondrial function during early lactation in dairy cows: Association with protein lysine acetylation, PloS One 14 (2019) e0213780. https://doi.org/10.1371/journal.pone.0213780.
• N. Lago, F.N. Kaufmann, M.L. Negro-Demontel, D. Alí-Ruiz, G. Ghisleni, N. Rego, A. Arcas-García, N. Vitureira, K. Jansen, L.M. Souza, R.A. Silva, D.R. Lara, B. Pannunzio, J.A. Abin-Carriquiry, J. Amo-Aparicio, C. Martin-Otal, H. Naya, D.B. McGavern, J. Sayós, R. López-Vales, M.P. Kaster, H. Peluffo, CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness, Proc. Natl. Acad. Sci. U.S.A. 117 (2020) 6651–6662. https://doi.org/10.1073/pnas.1911816117.
• M. Bresque, K. Cal, V. Pérez-Torrado, L. Colman, J. Rodríguez-Duarte, C. Vilaseca, L. Santos, M.P. Garat, S. Ruiz, F. Evans, R. Dapueto, P. Contreras, A. Calliari, C. Escande, SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice, Journal of Biological Chemistry 298 (2022) 101711. https://doi.org/10.1016/j.jbc.2022.101711.
• L. Santos, L. Colman, P. Contreras, C.C. Chini, A. Carlomagno, A. Leyva, M. Bresque, I. Marmisolle, C. Quijano, R. Duran, F. Irigoin, V. Prieto-Echague, M.H. Vendelbo, J.R. Sotelo-Silveira, E.N. Chini, J.L. Badano, A.J. Calliari, C. Escande, A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo, Scientific Reports 9 (2019) 14381. https://doi.org/10.1038/s41598-019-50789-7.
• C. Chavarria, S. Rodriguez-Bottero, C. Quijano, P. Cassina, J.M. Souza, Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte reactivity and toxicity to neurons, The Biochemical Journal 475 (2018) 3153–3169. https://doi.org/10.1042/BCJ20180297.
• P.V. Martino Adami, P. Galeano, M.L. Wallinger, C. Quijano, A. Rabossi, E.S. Pagano, N. Olivar, C. Reyes Toso, D. Cardinali, L.I. Brusco, S. Do Carmo, R. Radi, G. Gevorkian, E.M. Castano, A.C. Cuello, L. Morelli, Worsening of memory deficit induced by energy-dense diet in a rat model of early-Alzheimer's disease is associated to neurotoxic Abeta species and independent of neuroinflammation, Biochimica et Biophysica Acta. Molecular Basis of Disease 1863 (2017) 731–743. https://doi.org/10.1016/j.bbadis.2016.12.014.
• P.V. Martino Adami, C. Quijano, N. Magnani, P. Galeano, P. Evelson, A. Cassina, S. Do Carmo, M.C. Leal, E.M. Castano, A.C. Cuello, L. Morelli, Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease, Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 37 (2017) 69–84. https://doi.org/10.1177/0271678X15615132.
• F. Tomasina, J. Martínez, A. Zeida, M.L. Chiribao, V. Demicheli, A. Correa, C. Quijano, L. Castro, R.H. Carnahan, P. Vinson, M. Goff, T. Cooper, W.H. McDonald, N. Castellana, L. Hannibal, P.T. Morse, J. Wan, M. Hüttemann, R. Jemmerson, L. Piacenza, R. Radi, De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochrome c in cells, Proc. Natl. Acad. Sci. U.S.A. 119 (2022) e2213432119. https://doi.org/10.1073/pnas.2213432119.
• M. García-Roche, D. Talmón, G. Cañibe, A.L. Astessiano, A. Mendoza, C. Quijano, A. Cassina, M. Carriquiry, Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system, Journal of Dairy Science (2022) S0022030222003034. https://doi.org/10.3168/jds.2021-21358.
• M. García-Roche, G. Cañibe, A. Casal, D.A. Mattiauda, M. Ceriani, A. Jasinsky, A. Cassina, C. Quijano, M. Carriquiry, Glucose and Fatty Acid Metabolism of Dairy Cows in a Total Mixed Ration or Pasture-Based System During Lactation, Front. Anim. Sci. 2 (2021) 622500. https://doi.org/10.3389/fanim.2021.622500.
• L. Spangenberg, M. Grana, S. Mansilla, J. Martinez, A. Tapie, G. Greif, N. Montano, A. Vaglio, R. Guecaimburu, C. Robello, L. Castro, C. Quijano, V. Raggio, H. Naya, Deep sequencing discovery of causal mtDNA mutations in a patient with unspecific neurological disease, Mitochondrion 46 (2019) 337–344. https://doi.org/10.1016/j.mito.2018.09.004.
• L. Spangenberg, M. Graña, G. Greif, J.M. Suarez-Rivero, K. Krysztal, A. Tapié, M. Bodí, V. Fra, A. Lemes, R. Gueçaimburú, A. Cerisola, J.A. Sánchez-Alcázar, C. Robello, V. Raggio, H. Naya, 3697G N A in MT-ND1 is a causative mutation in mitochondrial disease, Mitochondrion 28 (2016) 54–59. https://doi.org/10.1016/j.mito.2016.03.006.