Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease.
Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease.
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DOI：
10.1038/s41598-021-82884-z
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发表时间：
2021-02-08
影响因子：
4.6
通讯作者：
Braet F
中科院分区：
文献类型：
--
作者：
Shami GJ;Cheng D;Verhaegh P;Koek G;Wisse E;Braet F
巨线粒体是肝实质细胞中形状特殊的超大型线粒体，其内部结构的特征是排列整齐的嵴、增大的基质颗粒和晶体内含物。在人体组织活检中存在巨大的线粒体通常与细胞逆境有关，这些细胞逆境是由酒精、外源性物质、抗癌药物、自由基等毒素、营养缺乏或高脂肪西方饮食引起的。非酒精性脂肪性肝病是目前最常见的脂质代谢异常的肝脏疾病，其中线粒体功能障碍起着至关重要的作用。目前尚不清楚巨大线粒体的形态特征是一种适应还是由这种功能障碍引起的。在本研究中，我们采用了一种互补的多模态成像方法，包括阵列断层扫描和透射电子断层扫描，以比较分析4例诊断为非酒精性脂肪肝患者的数千个正常和巨大线粒体的结构和形态参数。在这样做的过程中，我们揭示了功能改变与线粒体的线粒体，并提出了一个机制，其形成的基础上，我们的超微结构的研究结果。
Giant mitochondria are peculiarly shaped, extremely large mitochondria in hepatic parenchymal cells, the internal structure of which is characterised by atypically arranged cristae, enlarged matrix granules and crystalline inclusions. The presence of giant mitochondria in human tissue biopsies is often linked with cellular adversity, caused by toxins such as alcohol, xenobiotics, anti-cancer drugs, free-radicals, nutritional deficiencies or as a consequence of high fat Western diets. To date, non-alcoholic fatty liver disease is the most prevalent liver disease in lipid dysmetabolism, in which mitochondrial dysfunction plays a crucial role. It is not well understood whether the morphologic characteristics of giant mitochondria are an adaption or caused by such dysfunction. In the present study, we employ a complementary multimodal imaging approach involving array tomography and transmission electron tomography in order to comparatively analyse the structure and morphometric parameters of thousands of normal- and giant mitochondria in four patients diagnosed with non-alcoholic fatty liver disease. In so doing, we reveal functional alterations associated with mitochondrial gigantism and propose a mechanism for their formation based on our ultrastructural findings.
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影响因子：
4.6
作者：
Jiang YF;Lin SS;Chen JM;Tsai HZ;Hsieh TS;Fu CY
通讯作者：
Fu CY
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
DOI：
10.1016/0006-291x(63)90377-2
发表时间：
1963-01-01
影响因子：
3.1
作者：
LEHNINGER, AL;GREENAWAY, JW;ROSSI, CS
通讯作者：
ROSSI, CS
影响因子：
3.5
作者：
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通讯作者：
REZNICK, AZ
影响因子：
6
作者：
Cataldo, Anne M.;McPhie, Donna L.;Cohen, Bruce M.
通讯作者：
Cohen, Bruce M.