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Download fileThe mitochondrial genome in aging and disease and the future of mitochondrial therapeutics
journal contribution
posted on 2022-02-25, 09:37 authored by Sanjana Saravanan, Caitlin J Lewis, Bhavna Dixit, Matthew S O’Connor, Alexandra StolzingAlexandra Stolzing, Amutha BoominathanMitochondria 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
BiomedicinesVolume
10Issue
2Publisher
MDPI AGVersion
- VoR (Version of Record)
Rights holder
© the AuthorsPublisher 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
2022-02-16Publication date
2022-02-18Copyright date
2022eISSN
2227-9059Publisher version
Language
- en