iPSC models of mitochondrial diseases

Mitochondrial diseases are historically difficult to study. They cause multi-systemic defects with prevalent impairment of hard-to-access tissues such as the brain and the heart. Furthermore, they suffer from a paucity of conventional model systems, especially because of the challenges associated wi...

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Main Authors: Sonja Heiduschka, Alessandro Prigione
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125000385
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author Sonja Heiduschka
Alessandro Prigione
author_facet Sonja Heiduschka
Alessandro Prigione
author_sort Sonja Heiduschka
collection DOAJ
description Mitochondrial diseases are historically difficult to study. They cause multi-systemic defects with prevalent impairment of hard-to-access tissues such as the brain and the heart. Furthermore, they suffer from a paucity of conventional model systems, especially because of the challenges associated with mitochondrial DNA (mtDNA) engineering. Consequently, most mitochondrial diseases are currently untreatable. Human induced pluripotent stem cells (iPSCs) represent a promising approach for developing human model systems and assessing therapeutic avenues in a patient- and tissue-specific context. iPSCs are being increasingly used to investigate mitochondrial diseases, either for dissecting mutation-specific defects within two-dimensional (2D) or three-dimensional (3D) progenies or for unveiling the impact of potential treatment options. Here, we review how iPSC-derived 2D cells and 3D organoid models have been applied to the study of mitochondrial diseases caused by either nuclear or mtDNA defects. We anticipate that the field of iPSC-driven modeling of mitochondrial diseases will continue to grow, likely leading to the development of innovative platforms for treatment discovery and toxicity that could benefit the patient community suffering from these debilitating disorders with highly unmet medical needs.
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spelling doaj-art-6ca363d7b1114752b49ccee781dc3d2e2025-08-20T02:05:28ZengElsevierNeurobiology of Disease1095-953X2025-04-0120710682210.1016/j.nbd.2025.106822iPSC models of mitochondrial diseasesSonja Heiduschka0Alessandro Prigione1Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Germany; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, GermanyDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany; Corresponding author at: Department of General Pediatrics, Neonatology and Pediatric Cardiology, Duesseldorf University Hospital, Heinrich Heine University, Moorenstr. 5, 40225 Duesseldorf, Germany.Mitochondrial diseases are historically difficult to study. They cause multi-systemic defects with prevalent impairment of hard-to-access tissues such as the brain and the heart. Furthermore, they suffer from a paucity of conventional model systems, especially because of the challenges associated with mitochondrial DNA (mtDNA) engineering. Consequently, most mitochondrial diseases are currently untreatable. Human induced pluripotent stem cells (iPSCs) represent a promising approach for developing human model systems and assessing therapeutic avenues in a patient- and tissue-specific context. iPSCs are being increasingly used to investigate mitochondrial diseases, either for dissecting mutation-specific defects within two-dimensional (2D) or three-dimensional (3D) progenies or for unveiling the impact of potential treatment options. Here, we review how iPSC-derived 2D cells and 3D organoid models have been applied to the study of mitochondrial diseases caused by either nuclear or mtDNA defects. We anticipate that the field of iPSC-driven modeling of mitochondrial diseases will continue to grow, likely leading to the development of innovative platforms for treatment discovery and toxicity that could benefit the patient community suffering from these debilitating disorders with highly unmet medical needs.http://www.sciencedirect.com/science/article/pii/S0969996125000385Mitochondrial diseasesDisease modelingPluripotent stem cellsBrain organoidsDrug discovery
spellingShingle Sonja Heiduschka
Alessandro Prigione
iPSC models of mitochondrial diseases
Neurobiology of Disease
Mitochondrial diseases
Disease modeling
Pluripotent stem cells
Brain organoids
Drug discovery
title iPSC models of mitochondrial diseases
title_full iPSC models of mitochondrial diseases
title_fullStr iPSC models of mitochondrial diseases
title_full_unstemmed iPSC models of mitochondrial diseases
title_short iPSC models of mitochondrial diseases
title_sort ipsc models of mitochondrial diseases
topic Mitochondrial diseases
Disease modeling
Pluripotent stem cells
Brain organoids
Drug discovery
url http://www.sciencedirect.com/science/article/pii/S0969996125000385
work_keys_str_mv AT sonjaheiduschka ipscmodelsofmitochondrialdiseases
AT alessandroprigione ipscmodelsofmitochondrialdiseases