Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?

Mitochondria are specialized organelles involved in energy production that have retained their own genome throughout evolutionary history. The mitochondrial genome (mtDNA) is maternally inherited and requires coordinated regulation with nuclear genes to produce functional enzyme complexes that drive...

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Autores principales:	Jesse D. Moreira, Deepa M. Gopal, Darrell N. Kotton, Jessica L. Fetterman
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitochondria oxidative phosphorylation induced pluripotent stem cells heteroplasmy Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8c895a0ec7e5483496892b963e7c4dde
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spelling	oai:doaj.org-article:8c895a0ec7e5483496892b963e7c4dde2021-11-25T17:40:32ZGaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?10.3390/genes121116682073-4425https://doaj.org/article/8c895a0ec7e5483496892b963e7c4dde2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1668https://doaj.org/toc/2073-4425Mitochondria are specialized organelles involved in energy production that have retained their own genome throughout evolutionary history. The mitochondrial genome (mtDNA) is maternally inherited and requires coordinated regulation with nuclear genes to produce functional enzyme complexes that drive energy production. Each mitochondrion contains 5–10 copies of mtDNA and consequently, each cell has several hundreds to thousands of mtDNAs. Due to the presence of multiple copies of mtDNA in a mitochondrion, mtDNAs with different variants may co-exist, a condition called heteroplasmy. Heteroplasmic variants can be clonally expanded, even in post-mitotic cells, as replication of mtDNA is not tied to the cell-division cycle. Heteroplasmic variants can also segregate during germ cell formation, underlying the inheritance of some mitochondrial mutations. Moreover, the uneven segregation of heteroplasmic variants is thought to underlie the heterogeneity of mitochondrial variation across adult tissues and resultant differences in the clinical presentation of mitochondrial disease. Until recently, however, the mechanisms mediating the relation between mitochondrial genetic variation and disease remained a mystery, largely due to difficulties in modeling human mitochondrial genetic variation and diseases. The advent of induced pluripotent stem cells (iPSCs) and targeted gene editing of the nuclear, and more recently mitochondrial, genomes now provides the ability to dissect how genetic variation in mitochondrial genes alter cellular function across a variety of human tissue types. This review will examine the origins of mitochondrial heteroplasmic variation and propagation, and the tools used to model mitochondrial genetic diseases. Additionally, we discuss how iPSC technologies represent an opportunity to advance our understanding of human mitochondrial genetics in disease.Jesse D. MoreiraDeepa M. GopalDarrell N. KottonJessica L. FettermanMDPI AGarticlemitochondriaoxidative phosphorylationinduced pluripotent stem cellsheteroplasmyGeneticsQH426-470ENGenes, Vol 12, Iss 1668, p 1668 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria oxidative phosphorylation induced pluripotent stem cells heteroplasmy Genetics QH426-470
spellingShingle	mitochondria oxidative phosphorylation induced pluripotent stem cells heteroplasmy Genetics QH426-470 Jesse D. Moreira Deepa M. Gopal Darrell N. Kotton Jessica L. Fetterman Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
description	Mitochondria are specialized organelles involved in energy production that have retained their own genome throughout evolutionary history. The mitochondrial genome (mtDNA) is maternally inherited and requires coordinated regulation with nuclear genes to produce functional enzyme complexes that drive energy production. Each mitochondrion contains 5–10 copies of mtDNA and consequently, each cell has several hundreds to thousands of mtDNAs. Due to the presence of multiple copies of mtDNA in a mitochondrion, mtDNAs with different variants may co-exist, a condition called heteroplasmy. Heteroplasmic variants can be clonally expanded, even in post-mitotic cells, as replication of mtDNA is not tied to the cell-division cycle. Heteroplasmic variants can also segregate during germ cell formation, underlying the inheritance of some mitochondrial mutations. Moreover, the uneven segregation of heteroplasmic variants is thought to underlie the heterogeneity of mitochondrial variation across adult tissues and resultant differences in the clinical presentation of mitochondrial disease. Until recently, however, the mechanisms mediating the relation between mitochondrial genetic variation and disease remained a mystery, largely due to difficulties in modeling human mitochondrial genetic variation and diseases. The advent of induced pluripotent stem cells (iPSCs) and targeted gene editing of the nuclear, and more recently mitochondrial, genomes now provides the ability to dissect how genetic variation in mitochondrial genes alter cellular function across a variety of human tissue types. This review will examine the origins of mitochondrial heteroplasmic variation and propagation, and the tools used to model mitochondrial genetic diseases. Additionally, we discuss how iPSC technologies represent an opportunity to advance our understanding of human mitochondrial genetics in disease.
format	article
author	Jesse D. Moreira Deepa M. Gopal Darrell N. Kotton Jessica L. Fetterman
author_facet	Jesse D. Moreira Deepa M. Gopal Darrell N. Kotton Jessica L. Fetterman
author_sort	Jesse D. Moreira
title	Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
title_short	Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
title_full	Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
title_fullStr	Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
title_full_unstemmed	Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?
title_sort	gaining insight into mitochondrial genetic variation and downstream pathophysiology: what can i(pscs) do?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8c895a0ec7e5483496892b963e7c4dde
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_version_	1718412117217902592

Gaining Insight into Mitochondrial Genetic Variation and Downstream Pathophysiology: What Can i(PSCs) Do?

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