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

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journal contribution
posted on 25.02.2022, 09:37 by Sanjana Saravanan, Caitlin J Lewis, Bhavna Dixit, Matthew S O’Connor, Alexandra StolzingAlexandra Stolzing, Amutha Boominathan
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.

Funding

SENS Research Foundation

Foster Foundation

Forever Healthy Foundation

LifeSpan.io

Longecity Foundation

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Biomedicines

Volume

10

Issue

2

Publisher

MDPI AG

Version

VoR (Version of Record)

Rights holder

© the Authors

Publisher statement

This is an Open Access Article. It is published by MDPI under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

Acceptance date

16/02/2022

Publication date

2022-02-18

Copyright date

2022

eISSN

2227-9059

Language

en

Depositor

Prof Alexandra Stolzing. Deposit date: 25 February 2022

Article number

490