Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease

Abstract 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 biops...

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Autores principales:	Gerald J. Shami, Delfine Cheng, Pauline Verhaegh, Ger Koek, Eddie Wisse, Filip Braet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6eff5c13dbb24d7683b36c414e0888d2
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spelling	oai:doaj.org-article:6eff5c13dbb24d7683b36c414e0888d22021-12-02T14:26:54ZThree-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease10.1038/s41598-021-82884-z2045-2322https://doaj.org/article/6eff5c13dbb24d7683b36c414e0888d22021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82884-zhttps://doaj.org/toc/2045-2322Abstract 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.Gerald J. ShamiDelfine ChengPauline VerhaeghGer KoekEddie WisseFilip BraetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gerald J. Shami Delfine Cheng Pauline Verhaegh Ger Koek Eddie Wisse Filip Braet Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
description	Abstract 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.
format	article
author	Gerald J. Shami Delfine Cheng Pauline Verhaegh Ger Koek Eddie Wisse Filip Braet
author_facet	Gerald J. Shami Delfine Cheng Pauline Verhaegh Ger Koek Eddie Wisse Filip Braet
author_sort	Gerald J. Shami
title	Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
title_short	Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
title_full	Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
title_fullStr	Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
title_full_unstemmed	Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
title_sort	three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6eff5c13dbb24d7683b36c414e0888d2
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Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease

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