Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma Journal Article

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Authors: Lennon, F. E.; Cianci, G. C.; Kanteti, R.; Riehm, J. J.; Arif, Q.; Poroyko, V. A.; Lupovitch, E.; Vigneswaran, W; Husain, A.; Chen, P; Liao, J. K.; Sattler, M.; Kindler, H. L.; Salgia, R.
Article Title: Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma
Abstract: Malignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism. MM cell lines display a spectrum of altered mitochondrial morphologies and function compared to control mesothelial cells. Fractal dimension and lacunarity measurements are a sensitive and objective method to quantify mitochondrial morphology and most importantly are a promising predictor of response to mitochondrial inhibition. Control cells have high fractal dimension and low lacunarity and are relatively insensitive to mitochondrial inhibition. MM cells exhibit a spectrum of sensitivities to mitochondrial inhibitors. Low mitochondrial fractal dimension and high lacunarity correlates with increased sensitivity to the mitochondrial inhibitor metformin. Lacunarity also correlates with sensitivity to Mdivi-1, a mitochondrial fission inhibitor. MM and control cells have similar sensitivities to cisplatin, a chemotherapeutic agent used in the treatment of MM. Neither oxidative phosphorylation nor glycolytic activity, correlated with sensitivity to either metformin or mdivi-1. Our results suggest that mitochondrial inhibition may be an effective and selective therapeutic strategy in mesothelioma, and identifies mitochondrial morphology as a possible predictor of response to targeted mitochondrial inhibition.
Journal Title: Scientific reports
Volume: 6
ISSN: 2045-2322; 2045-2322
Publisher: Unknown  
Journal Place: England
Date Published: 2016
Start Page: 24578
Language: eng
DOI/URL:

10.1038/srep24578
Notes: LR: 20160520; GR: DK085006/DK/NIDDK NIH HHS/United States; GR: HL052233/HL/NHLBI NIH HHS/United States; GR: R01 HL052233/HL/NHLBI NIH HHS/United States; JID: 101563288; OID: NLM: PMC4832330; 2015/11/24 [received]; 2016/03/30 [accepted]; epublish