| Author | Caldwell, Stephen H. | |
| Author | Freitas, Luiz Antonio Rodrigues de | |
| Author | Park, Sang H. | |
| Author | Moreno, Maria Lúcia Vieira | |
| Author | Redick, Jan A. | |
| Author | Davis, Christine A. | |
| Author | Sisson, Barbee J. | |
| Author | Patrie, James T. | |
| Author | Cotrim, Helma Pinchemel | |
| Author | Argo, Curtis K. | |
| Author | Al-Osaimi, Abdullah | |
| Access date | 2014-06-11T14:20:44Z | |
| Available date | 2014-06-11T14:20:44Z | |
| Document date | 2009 | |
| Citation | CALDWELL, S. H. et al. Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis. Hepatology, v. 49, n. 6, p. 1888-1895, 2009. | pt_BR |
| ISSN | 1527-3350 | |
| URI | https://www.arca.fiocruz.br/handle/icict/7811 | |
| Language | eng | pt_BR |
| Publisher | Wiley InterScience | pt_BR |
| Rights | open access | pt_BR |
| Title | Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1002/hep.22851 | |
| 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. | pt_BR |
| Affilliation | Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA / GI/Hepatology. Hallym University Sacred Heart Hospital. Seoul, Korea. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Advanced Microscopy Center. Charlottesville, VA. | pt_BR |
| Affilliation | Advanced Microscopy Center. Charlottesville, VA | pt_BR |
| Affilliation | Advanced Microscopy Center. Charlottesville, VA. | pt_BR |
| Affilliation | Department of Outcomes Medicine. University of Virginia. Charlottesville, VA. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Division of GI/Hepatology. Salvador, BA, Brasil | pt_BR |
| Affilliation | Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA. | pt_BR |
| Affilliation | Division of GI/Hepatology. Department of Internal Medicine. Charlottesville, VA. | pt_BR |
| DeCS | Fígado Gorduroso/patologia | pt_BR |
| DeCS | Mitocôndrias/patologia | pt_BR |
| DeCS | Adulto | pt_BR |
| DeCS | Idoso | pt_BR |
| DeCS | Cristalização | pt_BR |
| DeCS | Feminino | pt_BR |
| DeCS | Humanos | pt_BR |
| DeCS | Meia-Idade | pt_BR |
| DeCS | Estudos Prospectivos | pt_BR |
| DeCS | Método Simples-Cego | pt_BR |
