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Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology

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Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. / Elouej, Sahar; Harhouri, Karim; Le Mao, Morgane; Baujat, Genevieve; Nampoothiri, Sheela; Kayserili, Hϋlya; Menabawy, Nihal Al; Selim, Laila; Paneque, Arianne Llamos; Kubisch, Christian; Lessel, Davor; Rubinsztajn, Robert; Charar, Chayki; Bartoli, Catherine; Airault, Coraline; Deleuze, Jean-François; Rötig, Agnes; Bauer, Peter; Pereira, Catarina; Loh, Abigail; Escande-Beillard, Nathalie; Muchir, Antoine; Martino, Lisa; Gruenbaum, Yosef; Lee, Song-Hua; Manivet, Philippe; Lenaers, Guy; Reversade, Bruno; Lévy, Nicolas; De Sandre-Giovannoli, Annachiara.

In: NAT COMMUN, Vol. 11, No. 1, 11.09.2020, p. 4589.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Elouej, S, Harhouri, K, Le Mao, M, Baujat, G, Nampoothiri, S, Kayserili, H, Menabawy, NA, Selim, L, Paneque, AL, Kubisch, C, Lessel, D, Rubinsztajn, R, Charar, C, Bartoli, C, Airault, C, Deleuze, J-F, Rötig, A, Bauer, P, Pereira, C, Loh, A, Escande-Beillard, N, Muchir, A, Martino, L, Gruenbaum, Y, Lee, S-H, Manivet, P, Lenaers, G, Reversade, B, Lévy, N & De Sandre-Giovannoli, A 2020, 'Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology', NAT COMMUN, vol. 11, no. 1, pp. 4589. https://doi.org/10.1038/s41467-020-18146-9

APA

Elouej, S., Harhouri, K., Le Mao, M., Baujat, G., Nampoothiri, S., Kayserili, H., Menabawy, N. A., Selim, L., Paneque, A. L., Kubisch, C., Lessel, D., Rubinsztajn, R., Charar, C., Bartoli, C., Airault, C., Deleuze, J-F., Rötig, A., Bauer, P., Pereira, C., ... De Sandre-Giovannoli, A. (2020). Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. NAT COMMUN, 11(1), 4589. https://doi.org/10.1038/s41467-020-18146-9

Vancouver

Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H et al. Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology. NAT COMMUN. 2020 Sep 11;11(1):4589. https://doi.org/10.1038/s41467-020-18146-9

Bibtex

@article{e1da6fbe70e44142ad84b463f29ae29b,
title = "Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology",
abstract = "Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients' primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.",
author = "Sahar Elouej and Karim Harhouri and {Le Mao}, Morgane and Genevieve Baujat and Sheela Nampoothiri and Hϋlya Kayserili and Menabawy, {Nihal Al} and Laila Selim and Paneque, {Arianne Llamos} and Christian Kubisch and Davor Lessel and Robert Rubinsztajn and Chayki Charar and Catherine Bartoli and Coraline Airault and Jean-Fran{\c c}ois Deleuze and Agnes R{\"o}tig and Peter Bauer and Catarina Pereira and Abigail Loh and Nathalie Escande-Beillard and Antoine Muchir and Lisa Martino and Yosef Gruenbaum and Song-Hua Lee and Philippe Manivet and Guy Lenaers and Bruno Reversade and Nicolas L{\'e}vy and {De Sandre-Giovannoli}, Annachiara",
year = "2020",
month = sep,
day = "11",
doi = "10.1038/s41467-020-18146-9",
language = "English",
volume = "11",
pages = "4589",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology

AU - Elouej, Sahar

AU - Harhouri, Karim

AU - Le Mao, Morgane

AU - Baujat, Genevieve

AU - Nampoothiri, Sheela

AU - Kayserili, Hϋlya

AU - Menabawy, Nihal Al

AU - Selim, Laila

AU - Paneque, Arianne Llamos

AU - Kubisch, Christian

AU - Lessel, Davor

AU - Rubinsztajn, Robert

AU - Charar, Chayki

AU - Bartoli, Catherine

AU - Airault, Coraline

AU - Deleuze, Jean-François

AU - Rötig, Agnes

AU - Bauer, Peter

AU - Pereira, Catarina

AU - Loh, Abigail

AU - Escande-Beillard, Nathalie

AU - Muchir, Antoine

AU - Martino, Lisa

AU - Gruenbaum, Yosef

AU - Lee, Song-Hua

AU - Manivet, Philippe

AU - Lenaers, Guy

AU - Reversade, Bruno

AU - Lévy, Nicolas

AU - De Sandre-Giovannoli, Annachiara

PY - 2020/9/11

Y1 - 2020/9/11

N2 - Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients' primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.

AB - Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients' primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.

U2 - 10.1038/s41467-020-18146-9

DO - 10.1038/s41467-020-18146-9

M3 - SCORING: Journal article

C2 - 32917887

VL - 11

SP - 4589

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -