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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/2/490 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T22:30:47Z |
| format | Article |
| id | doaj.art-409bea393f7144ba82b88627923cd094 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T22:30:47Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-409bea393f7144ba82b88627923cd0942023-11-23T18:56:24ZengMDPI AGBiomedicines2227-90592022-02-0110249010.3390/biomedicines10020490The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial TherapeuticsSanjana Saravanan0Caitlin J. Lewis1Bhavna Dixit2Matthew S. O’Connor3Alexandra Stolzing4Amutha Boominathan5Division of Mitochondria Biology, SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA 94041, USADivision of Mitochondria Biology, SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA 94041, USADivision of Mitochondria Biology, SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA 94041, USAUnderdog Pharmaceuticals Inc., 110 Pioneer Way, Suite J, Mountain View, CA 94041, USADivision of Mitochondria Biology, SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA 94041, USADivision of Mitochondria Biology, SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA 94041, USAMitochondria 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.https://www.mdpi.com/2227-9059/10/2/490mitochondriamtDNAmtDNA mutationsmitochondrial diseasesmtDNA editingallotopic expression |
| spellingShingle | 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 Biomedicines mitochondria mtDNA mtDNA mutations mitochondrial diseases mtDNA editing allotopic expression |
| title | 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_short | 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 |
| topic | mitochondria mtDNA mtDNA mutations mitochondrial diseases mtDNA editing allotopic expression |
| url | https://www.mdpi.com/2227-9059/10/2/490 |
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