The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics

Mitochondria are intracellular organelles that utilize nutrients to generate energy in the form of ATP by oxidative phosphorylation. Mitochondrial DNA (mtDNA) in humans is a 16,569 base pair double-stranded circular DNA that encodes for 13 vital proteins of the electron transport chain. Our understa...

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Main Authors: Sanjana Saravanan, Caitlin J Lewis, Bhavna Dixit, Matthew S O’Connor, Alexandra Stolzing, Amutha Boominathan
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Published: 2022
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Online Access:https://hdl.handle.net/2134/19234950.v1
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spelling rr-article-192349502022-02-18T00:00:00Z The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics Sanjana Saravanan (12136119) Caitlin J Lewis (12136122) Bhavna Dixit (12136125) Matthew S O’Connor (12136128) Alexandra Stolzing (1251348) Amutha Boominathan (12136131) gene therapy allotopic expression mtDNA editing mitochondrial diseases mtDNA mutations mtDNA mitochondria Mitochondria are intracellular organelles that utilize nutrients to generate energy in the form of ATP by oxidative phosphorylation. Mitochondrial DNA (mtDNA) in humans is a 16,569 base pair double-stranded circular DNA that encodes for 13 vital proteins of the electron transport chain. Our understanding of the mitochondrial genome’s transcription, translation, and maintenance is still emerging, and human pathologies caused by mtDNA dysfunction are widely observed. Additionally, a correlation between declining mitochondrial DNA quality and copy number with organelle dysfunction in aging is well-documented in the literature. Despite tremendous advancements in nuclear gene-editing technologies and their value in translational avenues, our ability to edit mitochondrial DNA is still limited. In this review, we discuss the current therapeutic landscape in addressing the various pathologies that result from mtDNA mutations. We further evaluate existing gene therapy efforts, particularly allotopic expression and its potential to become an indispensable tool for restoring mitochondrial health in disease and aging. 2022-02-18T00:00:00Z Text Journal contribution 2134/19234950.v1 https://figshare.com/articles/journal_contribution/The_mitochondrial_genome_in_aging_and_disease_and_the_future_of_mitochondrial_therapeutics/19234950 CC BY 4.0
institution Loughborough University
collection Figshare
topic gene therapy
allotopic expression
mtDNA editing
mitochondrial diseases
mtDNA mutations
mtDNA
mitochondria
spellingShingle gene therapy
allotopic expression
mtDNA editing
mitochondrial diseases
mtDNA mutations
mtDNA
mitochondria
Sanjana Saravanan
Caitlin J Lewis
Bhavna Dixit
Matthew S O’Connor
Alexandra Stolzing
Amutha Boominathan
The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
description Mitochondria are intracellular organelles that utilize nutrients to generate energy in the form of ATP by oxidative phosphorylation. Mitochondrial DNA (mtDNA) in humans is a 16,569 base pair double-stranded circular DNA that encodes for 13 vital proteins of the electron transport chain. Our understanding of the mitochondrial genome’s transcription, translation, and maintenance is still emerging, and human pathologies caused by mtDNA dysfunction are widely observed. Additionally, a correlation between declining mitochondrial DNA quality and copy number with organelle dysfunction in aging is well-documented in the literature. Despite tremendous advancements in nuclear gene-editing technologies and their value in translational avenues, our ability to edit mitochondrial DNA is still limited. In this review, we discuss the current therapeutic landscape in addressing the various pathologies that result from mtDNA mutations. We further evaluate existing gene therapy efforts, particularly allotopic expression and its potential to become an indispensable tool for restoring mitochondrial health in disease and aging.
format Default
Article
author Sanjana Saravanan
Caitlin J Lewis
Bhavna Dixit
Matthew S O’Connor
Alexandra Stolzing
Amutha Boominathan
author_facet Sanjana Saravanan
Caitlin J Lewis
Bhavna Dixit
Matthew S O’Connor
Alexandra Stolzing
Amutha Boominathan
author_sort Sanjana Saravanan (12136119)
title The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
title_short The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
title_full The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
title_fullStr The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
title_full_unstemmed The mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
title_sort mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
publishDate 2022
url https://hdl.handle.net/2134/19234950.v1
_version_ 1797095214438940672