Ultrastructural identification of light microscopic giant mitochondria in alcoholic liver disease

Inagaki, T.; Kobayashi, Susumu; Ozeki, Norio; Suzuki, Masahiro; Fukuzawa, Yoshitaka; Shimizu, Kazuhito; Kato, Katsuhisa; Kato, Koichi

doi:10.1002/hep.1840150110

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…Results from this study now suggest that NO (µ m concentration) may have an additional neurotoxic mechanism by altering mitochondria motility during hypoxia. Alterations in mitochondrial morphology have been reported during hypoxia–ischemia and during acute glutamate exposure (Djaldetti 1982; Inagaki et al . 1992; Arbustini et al .…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia

Zanelli¹,

Trimmer

Solenski

2006

Journal of Neurochemistry

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Cortical nitric oxide (NO) production increases during hypoxia/ischemia in the immature brain and is associated with both neurotoxicity and mitochondrial dysfunction. Mitochondrial redistribution within the cell is critical to normal neuronal function, however, the effects of hypoxia on mitochondrial dynamics are not known. This study tested the hypothesis that hypoxia impairs mitochondrial movement via NO-mediated pathways. Fluorescently labeled mitochondria were studied using time-lapse digital video microscopy in cultured cortical neurons exposed either to hypoxia/re-oxygenation or to diethyleneamine/nitric oxide adduct, DETA-NO (100-500 lM). Two NO synthase inhibitors, were used to determine NO specificity. Mitochondrial mean velocity, the percentage of movement (i.e. the time spent moving) and mitochondrial morphology were analyzed. Exposure to hypoxia reduced mitochondrial movement to 10.4 ± 1.3% at 0 h and 7.4 ± 1.7% at 1 h of re-oxygenation, versus 25.6 ± 1.4% in controls (p < 0.05). Mean mitochondrial velocity (lm s )1 ) decreased from 0.374 ± 0.01 in controls to 0.146 ± 0.01 at 0 h and 0.177 ± 0.02 at 1 h of re-oxygenation (p < 0.001). Exposure to DETA-NO resulted in a significant decrease in mean mitochondrial velocity at all tested time points. Treatment with N G -nitro-L-arginine methyl ester (L-NAME) prevented the hypoxia-induced decrease in mitochondrial movement at 0 h (30.1 ± 1.6%) and at 1 h (26.1 ± 9%) of re-oxygenation. Exposure to either hypoxia/ re-oxygenation or NO also resulted in the rapid decrease in mitochondrial size. Both hypoxia and NO exposure result in impaired mitochondrial movement and morphology in cultured cortical neurons. As the effect of hypoxia on mitochondrial movement and morphology can be partially prevented by a nitric oxide synthase (NOS) inhibitor, these data suggest that an NO-mediated pathway is at least partially involved. Keywords: axonal transport, hypoxia, mitochondria, nitric oxide, nitric oxide synthase inhibitor, trafficking. Address correspondence and reprint requests to Nina J. Solenski MD, Department of Neurology, Box 800394, University of Virginia Health System, Charlottesville, VA 22908, USA. E-mail: njs2j@virginia.eduAbbreviations used: APAF-1, apoptosis protease-activating factor 1; DETA-NO, diethyleneamine/nitric oxide adduct; MK-801, dizocilpine maleate; L-NAME, N G -nitro-L-arginine methyl ester; 7-NiNa, 7-nitroindazole; NO, nitric oxide; NOS, nitric oxide synthase; PBS, phosphatebuffered saline; PI, propidium iodide; pO 2 , pressure of O 2 .

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Section: Discussionmentioning

confidence: 99%

Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia

Zanelli¹,

Trimmer

Solenski

2006

Journal of Neurochemistry

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“…Microscopic studies of live cells have revealed that these mitochondrial networks are extremely dynamic, with tubular processes undergoing frequent fragmentation, branching, and fusion, as well as redistribution within the cytoplasm (Bereiter-Hahn, 1990; Koning et ai., 1993). In addition to the dynamic properties of mitochondria found in most types of cells, certain pathological conditions lead to gross changes in mitochondrial morphology, including the development of giant mitochondria (Tandler and Hoppel, 1986;Inagaki et al, 1992). The molecular bases for these changes in mitochondrial morphology and distribution in both normal and diseased cells are unknown.…”

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confidence: 99%

Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.

Sogo

Yaffe

1994

The Journal of Cell Biology

269

232

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Abstract. Yeast cells with the mdm/0 mutation possess giant spherical mitochondria and are defective for mitochondrial inheritance. The giant mitochondria display classical features of mitochondrial ultrastructure, yet they appear incapable of movement or division. Genetic analysis indicated that the mutant phenotypes resulted from a single nuclear mutation, and the isolated MDMIO gene restored wild-type mitochondrial distribution and morphology when introduced into mutant cells. MDMIO encodes a protein of 56.2 kD located in the mitochondrial outer membrane. Depletion of Mdml0p from cells led to a condensation of normally extended, tubular mitochondria into giant spheres, and reexpression of the protein resulted in a rapid restoration of normal mitochondrial morphology. These results demonstrate that Mdml0p can control mitochondrial morphology, and that it plays a role in the inheritance of mitochondria. MITOCHONDRIAL inheritance is an essential component of cell proliferation (Yaffe, 1991b). This inheritance requires the growth and division of preexisting mitochondria and the distribution of mitochondria between daughter cells before cell division (Attardi and Schatz, 1988). Cytoskeletal elements have been implicated in the positioning and movement of mitochondria (Heggeness et al., 1978;Chen, 1988;McConnell and Yaffe, 1992;Drubin et al., 1993), but mechanisms underlying mitochondrial inheritance are poorly understood.Mitochondria are usually found as snakelike tubules, widely distributed in the eukaryotic cytoplasm (Tzagoloff, 1982;Bereiter-Hahn, 1990). Often, these tubules are interconnected into extended mitochondrial reticula (Stevens, 1981;Chen, 1988). Microscopic studies of live cells have revealed that these mitochondrial networks are extremely dynamic, with tubular processes undergoing frequent fragmentation, branching, and fusion, as well as redistribution within the cytoplasm (Bereiter-Hahn, 1990; Koning et ai., 1993). In addition to the dynamic properties of mitochondria found in most types of cells, certain pathological conditions lead to gross changes in mitochondrial morphology, including the development of giant mitochondria (Tandler and Hoppel, 1986;Inagaki et al., 1992). The molecular bases for these changes in mitochondrial morphology and distribution in both normal and diseased cells are unknown.We recently described several Saccharomyces cerevisiae mutants defective for mitochondrial inheritance (McConnell et al., 1990). These mitochondrial distribution and morphology (mdm) I mutants were identified by screening collections of temperature-sensitive strains by fluorescence microscopy for cells that failed to transfer mitochondria into daughter buds during incubation at the nonpermissive temperature. Analysis of two of these mutant strains led to the identification of a novel cytoskeletal component that mediates mitochondrial inheritance Yaffe, 1992, 1993), and it indicated a role for unsaturated fatty acids in mitochondrial movement (Stewart and Yaffe, 1991). Here, we describe a new mdm m...

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“…The significant difference between protein globules and the six bodies above is that protein globules contain immunoglobulin IgG, IgM, IgA, Fib and C3d, whereas the latter six do not. Huge mitochondria are round eosinophilic bodies with hematoxylin and eosin in liver cytoplasm, and are mitochondrial structures identified by electron microscopic examination [33]. Mallory bodies are irregular eosinophilic clumps with hematoxylin and eosin in liver cytoplasm, and are protein aggregates where the intermediate filament combines with ubiquitin.…”

Section: The Identification Of Protein Globules and Other Similar Bodmentioning

confidence: 99%

Protein Globule Formation in the Liver Graft during Cold Preservation for Liver Transplantation: Its Clinical and Pathological Significance

Feng¹,

He²,

Huang³

et al. 2013

OJPathology

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In liver transplantation, liver graft ischemia-reperfusion injury occurs mainly due to cold preservation and warm reperfusion. In this research, we study the affection of plasma protein of the donor on liver graft during cold preservation and warm reperfusion. In this study, 34 liver transplantations were performed from 2007 to 2010, and the clinical data were collected retrospectively from the Dongfang Hospital database. 34 specimens were harvested from 34 liver grafts when graft trimming as Group A and 34 specimens harvested from the same 34 liver grafts during liver transplantation surgery but before abdominal closure as B group. All liver tissue specimens were fixed with 40 g/L neutral formalin, embedded in paraffin. Light microscopy, transmission electron microscopy, Periodic Acid-Schiff (PAS) stain and immunohistochemical stain of IgG, IgM, IgA, C3d, C4d, Fib, C1q, and CD61 were used. In this study, we found that eosinophilic bodies emerged in liver lobes during liver transplantation which had not been reported previously in the literature. 1) Protein globules were found exclusively in liver graft specimens. The globules were round or oval with sharp edges, measured approximately 1.59 to 9.41 µm in diameter, and were scattered in the liver sinusoids or space of Disse or hepatocyte cytoplasm, were stained with IgG, IgM, IgA, Fib, C3d by immunohistochemical staining; 2) There was no statistical significant difference of protein globules number between A group and B group (P > 0.05); 3) IRI score of B group was not correlated with protein globules number (P > 0.05). Protein globules contain plasma composition, and may form during cold preservation.

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Ultrastructural identification of light microscopic giant mitochondria in alcoholic liver disease

Cited by 13 publications

References 14 publications

Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia

Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia

Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.

Protein Globule Formation in the Liver Graft during Cold Preservation for Liver Transplantation: Its Clinical and Pathological Significance

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