Cargando…
Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome
Barth syndrome (BTHS, OMIM 302060) is a genetic disorder caused by variants of the TAFAZZIN gene (G 4.5, OMIM 300394). This debilitating disorder is characterized by cardio- and skeletal myopathy, exercise intolerance, and neutropenia. TAFAZZIN is a transacylase that catalyzes the second step in the...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184736/ https://www.ncbi.nlm.nih.gov/pubmed/35693555 http://dx.doi.org/10.3389/fmolb.2022.915301 |
_version_ | 1784724591811231744 |
---|---|
author | Liang, Zhuqing Schmidtke, Michael W. Greenberg, Miriam L. |
author_facet | Liang, Zhuqing Schmidtke, Michael W. Greenberg, Miriam L. |
author_sort | Liang, Zhuqing |
collection | PubMed |
description | Barth syndrome (BTHS, OMIM 302060) is a genetic disorder caused by variants of the TAFAZZIN gene (G 4.5, OMIM 300394). This debilitating disorder is characterized by cardio- and skeletal myopathy, exercise intolerance, and neutropenia. TAFAZZIN is a transacylase that catalyzes the second step in the cardiolipin (CL) remodeling pathway, preferentially converting saturated CL species into unsaturated CLs that are susceptible to oxidation. As a hallmark mitochondrial membrane lipid, CL has been shown to be essential in a myriad of pathways, including oxidative phosphorylation, the electron transport chain, intermediary metabolism, and intrinsic apoptosis. The pathological severity of BTHS varies substantially from one patient to another, even in individuals bearing the same TAFAZZIN variant. The physiological modifier(s) leading to this disparity, along with the exact molecular mechanism linking CL to the various pathologies, remain largely unknown. Elevated levels of reactive oxygen species (ROS) have been identified in numerous BTHS models, ranging from yeast to human cell lines, suggesting that cellular ROS accumulation may participate in the pathogenesis of BTHS. Although the exact mechanism of how oxidative stress leads to pathogenesis is unknown, it is likely that CL oxidation plays an important role. In this review, we outline what is known about CL oxidation and provide a new perspective linking the functional relevance of CL remodeling and oxidation to ROS mitigation in the context of BTHS. |
format | Online Article Text |
id | pubmed-9184736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91847362022-06-11 Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome Liang, Zhuqing Schmidtke, Michael W. Greenberg, Miriam L. Front Mol Biosci Molecular Biosciences Barth syndrome (BTHS, OMIM 302060) is a genetic disorder caused by variants of the TAFAZZIN gene (G 4.5, OMIM 300394). This debilitating disorder is characterized by cardio- and skeletal myopathy, exercise intolerance, and neutropenia. TAFAZZIN is a transacylase that catalyzes the second step in the cardiolipin (CL) remodeling pathway, preferentially converting saturated CL species into unsaturated CLs that are susceptible to oxidation. As a hallmark mitochondrial membrane lipid, CL has been shown to be essential in a myriad of pathways, including oxidative phosphorylation, the electron transport chain, intermediary metabolism, and intrinsic apoptosis. The pathological severity of BTHS varies substantially from one patient to another, even in individuals bearing the same TAFAZZIN variant. The physiological modifier(s) leading to this disparity, along with the exact molecular mechanism linking CL to the various pathologies, remain largely unknown. Elevated levels of reactive oxygen species (ROS) have been identified in numerous BTHS models, ranging from yeast to human cell lines, suggesting that cellular ROS accumulation may participate in the pathogenesis of BTHS. Although the exact mechanism of how oxidative stress leads to pathogenesis is unknown, it is likely that CL oxidation plays an important role. In this review, we outline what is known about CL oxidation and provide a new perspective linking the functional relevance of CL remodeling and oxidation to ROS mitigation in the context of BTHS. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9184736/ /pubmed/35693555 http://dx.doi.org/10.3389/fmolb.2022.915301 Text en Copyright © 2022 Liang, Schmidtke and Greenberg. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Liang, Zhuqing Schmidtke, Michael W. Greenberg, Miriam L. Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title | Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title_full | Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title_fullStr | Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title_full_unstemmed | Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title_short | Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome |
title_sort | current knowledge on the role of cardiolipin remodeling in the context of lipid oxidation and barth syndrome |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184736/ https://www.ncbi.nlm.nih.gov/pubmed/35693555 http://dx.doi.org/10.3389/fmolb.2022.915301 |
work_keys_str_mv | AT liangzhuqing currentknowledgeontheroleofcardiolipinremodelinginthecontextoflipidoxidationandbarthsyndrome AT schmidtkemichaelw currentknowledgeontheroleofcardiolipinremodelinginthecontextoflipidoxidationandbarthsyndrome AT greenbergmiriaml currentknowledgeontheroleofcardiolipinremodelinginthecontextoflipidoxidationandbarthsyndrome |