Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target

E. M. M. Abdelwahab; S. Pal; K. Kvell; V. Sarosi; P. Bai; R. Rue; V. Krymskaya; D. McPhail; A. Porter; J. E. Pongracz

doi:10.1038/s41388-018-0625-1

Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target

E. M. M. Abdelwahab, S. Pal, K. Kvell, V. Sarosi, P. Bai, R. Rue, V. Krymskaya, D. McPhail, A. Porter, J. E. Pongracz (Corresponding Author)

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Abstract

Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.

Original language	English
Pages (from-to)	3093-3101
Number of pages	9
Journal	Oncogene
Volume	38
Early online date	20 Dec 2018
DOIs	https://doi.org/10.1038/s41388-018-0625-1
Publication status	Published - 2019

Keywords

BIOGENESIS
CELL
CHAIN
CYTOCHROME-C
ESTROGEN
FEATURES
GENE
PHOSPHORYLATION
TSC2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target
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Cite this

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title = "Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target",

abstract = "Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.",

keywords = "BIOGENESIS, CELL, CHAIN, CYTOCHROME-C, ESTROGEN, FEATURES, GENE, PHOSPHORYLATION, TSC2",

author = "Abdelwahab, {E. M. M.} and S. Pal and K. Kvell and V. Sarosi and P. Bai and R. Rue and V. Krymskaya and D. McPhail and A. Porter and Pongracz, {J. E.}",

note = "Acknowledgements The authors are grateful to Prof. Dr. Laszlo Seress, Professor Emeritus, Central Electron Microscope Laboratory, University of Pecs, Pecs, Hungary for his invaluable assistance with electron microscopic studies using the Jeol 1200 TEM and Jeol 1400 TEM electron microscopes. Jeol TEM was funded by the GINOP-2.3.3-15-2016-0002 (New generation electron microscope: 3D ultrastructure). We would also like to thank Dr. Veronika Csongei, PhD, Senior Lecturer, Department of Pharmaceutical Biotechnology and Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary for assistance with statistical analysis. Funding JEP was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of T{\'A}MOP-4.2.4.A/2-11/1-2012-0001 “National Excellence Program”.",

year = "2019",

doi = "10.1038/s41388-018-0625-1",

language = "English",

volume = "38",

pages = "3093--3101",

journal = "Oncogene",

issn = "0950-9232",

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AU - Abdelwahab, E. M. M.

AU - Pal, S.

AU - Kvell, K.

AU - Sarosi, V.

AU - Bai, P.

AU - Rue, R.

AU - Krymskaya, V.

AU - McPhail, D.

AU - Porter, A.

AU - Pongracz, J. E.

N1 - Acknowledgements The authors are grateful to Prof. Dr. Laszlo Seress, Professor Emeritus, Central Electron Microscope Laboratory, University of Pecs, Pecs, Hungary for his invaluable assistance with electron microscopic studies using the Jeol 1200 TEM and Jeol 1400 TEM electron microscopes. Jeol TEM was funded by the GINOP-2.3.3-15-2016-0002 (New generation electron microscope: 3D ultrastructure). We would also like to thank Dr. Veronika Csongei, PhD, Senior Lecturer, Department of Pharmaceutical Biotechnology and Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary for assistance with statistical analysis. Funding JEP was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 “National Excellence Program”.

PY - 2019

Y1 - 2019

N2 - Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.

AB - Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.

KW - BIOGENESIS

KW - CELL

KW - CHAIN

KW - CYTOCHROME-C

KW - ESTROGEN

KW - FEATURES

KW - GENE

KW - PHOSPHORYLATION

KW - TSC2

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JF - Oncogene

SN - 0950-9232

ER -

Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target

Abstract

Keywords

UN SDGs

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