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

• Published in: Oncogene Vol. 38; no. 16; pp. 3093 - 3101
• Main Authors: Abdelwahab, E. M. M., Pal, S., Kvell, K., Sarosi, V., Bai, P., Rue, R., Krymskaya, V., McPhail, D., Porter, A., Pongracz, J. E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2019; Nature Publishing Group
• Subjects: 13/105; 13/106; 13/31; 14/28; 38/77; 38/79; 45/61; 45/90; 631/154/555; 631/80/39; 96/34; 96/47; 96/63; Apoptosis; Auranofin; Biosynthesis; Brief Communication; Cell Biology; Cell Line, Tumor; Cell lines; Cell Proliferation - physiology; Complications and side effects; Development and progression; Disease Progression; Dosage and administration; Female; Health aspects; Human Genetics; Humans; Internal Medicine; Lung - pathology; Lung Neoplasms - pathology; Lung transplantation; Lymphangioleiomyomatosis - pathology; Medical schools; Medicine; Medicine & Public Health; Mitochondria; Mitochondria - pathology; Mitochondrial diseases; Mitochondrial Diseases - pathology; Oncology; Organ transplantation; Rapamycin; Rare diseases; Rare Diseases - pathology; Respiratory function; Risk factors; Smooth muscle; Surgery; Therapeutic applications; Young women
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0625-1

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.