Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7811
Title: Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis
Authors: Caldwell, Stephen H.
Freitas, Luiz Antonio Rodrigues de
Park, Sang H.
Moreno, Maria Lúcia Vieira
Redick, Jan A.
Davis, Christine A.
Sisson, Barbee J.
Patrie, James T.
Cotrim, Helma Pinchemel
Argo, Curtis K.
Al-Osaimi, Abdullah
Affilliation: Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.
Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA / GI/Hepatology. Hallym University Sacred Heart Hospital. Seoul, Korea.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.
Advanced Microscopy Center. Charlottesville, VA.
Advanced Microscopy Center. Charlottesville, VA
Advanced Microscopy Center. Charlottesville, VA.
Department of Outcomes Medicine. University of Virginia. Charlottesville, VA.
Universidade Federal da Bahia. Division of GI/Hepatology. Salvador, BA, Brasil
Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA.
Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA.
Abstract: Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well-documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well-known but little-studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). Conclusion: These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition.
DeCS: Fígado Gorduroso/patologia
Mitocôndrias/patologia
Adulto
Idoso
Cristalização
Feminino
Humanos
Meia-Idade
Estudos Prospectivos
Método Simples-Cego
Issue Date: 2009
Publisher: Wiley InterScience
Citation: CALDWELL, S. H. et al. Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis. Hepatology, v. 49, n. 6, p. 1888-1895, 2009.
DOI: 10.1002/hep.22851
ISSN: 1527-3350
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
Caldwell SH Intramitochondrial....pdf696.64 kBAdobe PDFThumbnail
View/Open



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.