Cargando…

Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology

Mitochondrial medicine is an exciting and rapidly evolving field. While the mitochondrial genome is small and differs from the nuclear genome in that it is circular and free of histones, it has been implicated in neurodegenerative diseases, type 2 diabetes, aging and cardiovascular disorders. Curren...

Descripción completa

Detalles Bibliográficos
Autores principales: Kargaran, Parisa K., Mosqueira, Diogo, Kozicz, Tamas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874022/
https://www.ncbi.nlm.nih.gov/pubmed/33585579
http://dx.doi.org/10.3389/fcvm.2020.604581
_version_ 1783649501160931328
author Kargaran, Parisa K.
Mosqueira, Diogo
Kozicz, Tamas
author_facet Kargaran, Parisa K.
Mosqueira, Diogo
Kozicz, Tamas
author_sort Kargaran, Parisa K.
collection PubMed
description Mitochondrial medicine is an exciting and rapidly evolving field. While the mitochondrial genome is small and differs from the nuclear genome in that it is circular and free of histones, it has been implicated in neurodegenerative diseases, type 2 diabetes, aging and cardiovascular disorders. Currently, there is a lack of efficient treatments for mitochondrial diseases. This has promoted the need for developing an appropriate platform to investigate and target the mitochondrial genome. However, developing these therapeutics requires a model system that enables rapid and effective studying of potential candidate therapeutics. In the past decade, induced pluripotent stem cells (iPSCs) have become a promising technology for applications in basic science and clinical trials, and have the potential to be transformative for mitochondrial drug development. Engineered iPSC-derived cardiomyocytes (iPSC-CM) offer a unique tool to model mitochondrial disorders. Additionally, these cellular models enable the discovery and testing of novel therapeutics and their impact on pathogenic mtDNA variants and dysfunctional mitochondria. Herein, we review recent advances in iPSC-CM models focused on mitochondrial dysfunction often causing cardiovascular diseases. The importance of mitochondrial disease systems biology coupled with genetically encoded NAD(+)/NADH sensors is addressed toward developing an in vitro translational approach to establish effective therapies.
format Online
Article
Text
id pubmed-7874022
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78740222021-02-11 Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology Kargaran, Parisa K. Mosqueira, Diogo Kozicz, Tamas Front Cardiovasc Med Cardiovascular Medicine Mitochondrial medicine is an exciting and rapidly evolving field. While the mitochondrial genome is small and differs from the nuclear genome in that it is circular and free of histones, it has been implicated in neurodegenerative diseases, type 2 diabetes, aging and cardiovascular disorders. Currently, there is a lack of efficient treatments for mitochondrial diseases. This has promoted the need for developing an appropriate platform to investigate and target the mitochondrial genome. However, developing these therapeutics requires a model system that enables rapid and effective studying of potential candidate therapeutics. In the past decade, induced pluripotent stem cells (iPSCs) have become a promising technology for applications in basic science and clinical trials, and have the potential to be transformative for mitochondrial drug development. Engineered iPSC-derived cardiomyocytes (iPSC-CM) offer a unique tool to model mitochondrial disorders. Additionally, these cellular models enable the discovery and testing of novel therapeutics and their impact on pathogenic mtDNA variants and dysfunctional mitochondria. Herein, we review recent advances in iPSC-CM models focused on mitochondrial dysfunction often causing cardiovascular diseases. The importance of mitochondrial disease systems biology coupled with genetically encoded NAD(+)/NADH sensors is addressed toward developing an in vitro translational approach to establish effective therapies. Frontiers Media S.A. 2021-01-18 /pmc/articles/PMC7874022/ /pubmed/33585579 http://dx.doi.org/10.3389/fcvm.2020.604581 Text en Copyright © 2021 Kargaran, Mosqueira and Kozicz. http://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 Cardiovascular Medicine
Kargaran, Parisa K.
Mosqueira, Diogo
Kozicz, Tamas
Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title_full Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title_fullStr Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title_full_unstemmed Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title_short Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
title_sort mitochondrial medicine: genetic underpinnings and disease modeling using induced pluripotent stem cell technology
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874022/
https://www.ncbi.nlm.nih.gov/pubmed/33585579
http://dx.doi.org/10.3389/fcvm.2020.604581
work_keys_str_mv AT kargaranparisak mitochondrialmedicinegeneticunderpinningsanddiseasemodelingusinginducedpluripotentstemcelltechnology
AT mosqueiradiogo mitochondrialmedicinegeneticunderpinningsanddiseasemodelingusinginducedpluripotentstemcelltechnology
AT kozicztamas mitochondrialmedicinegeneticunderpinningsanddiseasemodelingusinginducedpluripotentstemcelltechnology