Targeting Mitochondrial Function with Chemoptogenetics
Mitochondria are ATP-generating organelles in eukaryotic cells that produce reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS). Mitochondrial DNA (mtDNA) is packaged within nucleoids and, due to its close proximity to ROS production, endures oxidative base damage. This damage ca...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/10/2459 |
| _version_ | 1797475096675221504 |
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| author | Amy Romesberg Bennett Van Houten |
| author_facet | Amy Romesberg Bennett Van Houten |
| author_sort | Amy Romesberg |
| collection | DOAJ |
| description | Mitochondria are ATP-generating organelles in eukaryotic cells that produce reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS). Mitochondrial DNA (mtDNA) is packaged within nucleoids and, due to its close proximity to ROS production, endures oxidative base damage. This damage can be repaired by base excision repair (BER) within the mitochondria, or it can be degraded via exonucleases or mitophagy. Persistent mtDNA damage may drive the production of dysfunctional OXPHOS components that generate increased ROS, or OXPHOS components may be directly damaged by ROS, which then can cause more mtDNA damage and create a vicious cycle of ROS production and mitochondrial dysfunction. If mtDNA damage is left unrepaired, mtDNA mutations including deletions can result. The accumulation of mtDNA mutations has been associated with conditions ranging from the aging process to cancer and neurodegenerative conditions, but the sequence of events leading to mtDNA mutations and deletions is yet unknown. Researchers have utilized many systems and agents for generating ROS in mitochondria to observe the downstream effects on mtDNA, ROS, and mitochondrial function; yet, there are various drawbacks to these methodologies that limit their precision. Here, we describe a novel chemoptogenetic approach to target oxidative damage to mitochondria and mtDNA with a high spatial and temporal resolution so that the downstream effects of ROS-induced damage can be measured with a high precision in order to better understand the mechanism of mitochondrial dysfunction in aging, cancer, and neurodegenerative diseases. |
| first_indexed | 2024-03-09T20:39:19Z |
| format | Article |
| id | doaj.art-ce6e30b0fe9a4051afc912e65c40d193 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:39:19Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ce6e30b0fe9a4051afc912e65c40d1932023-11-23T23:03:24ZengMDPI AGBiomedicines2227-90592022-10-011010245910.3390/biomedicines10102459Targeting Mitochondrial Function with ChemoptogeneticsAmy Romesberg0Bennett Van Houten1Department of Biological Sciences, College of Arts and Sciences, Carlow University, 3333 Fifth Avenue, Pittsburgh, PA 15213, USAUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USAMitochondria are ATP-generating organelles in eukaryotic cells that produce reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS). Mitochondrial DNA (mtDNA) is packaged within nucleoids and, due to its close proximity to ROS production, endures oxidative base damage. This damage can be repaired by base excision repair (BER) within the mitochondria, or it can be degraded via exonucleases or mitophagy. Persistent mtDNA damage may drive the production of dysfunctional OXPHOS components that generate increased ROS, or OXPHOS components may be directly damaged by ROS, which then can cause more mtDNA damage and create a vicious cycle of ROS production and mitochondrial dysfunction. If mtDNA damage is left unrepaired, mtDNA mutations including deletions can result. The accumulation of mtDNA mutations has been associated with conditions ranging from the aging process to cancer and neurodegenerative conditions, but the sequence of events leading to mtDNA mutations and deletions is yet unknown. Researchers have utilized many systems and agents for generating ROS in mitochondria to observe the downstream effects on mtDNA, ROS, and mitochondrial function; yet, there are various drawbacks to these methodologies that limit their precision. Here, we describe a novel chemoptogenetic approach to target oxidative damage to mitochondria and mtDNA with a high spatial and temporal resolution so that the downstream effects of ROS-induced damage can be measured with a high precision in order to better understand the mechanism of mitochondrial dysfunction in aging, cancer, and neurodegenerative diseases.https://www.mdpi.com/2227-9059/10/10/2459mitochondrial DNAchemoptogeneticsmitochondrial dysfunctionmitochondriabase excision repairreactive oxygen species |
| spellingShingle | Amy Romesberg Bennett Van Houten Targeting Mitochondrial Function with Chemoptogenetics Biomedicines mitochondrial DNA chemoptogenetics mitochondrial dysfunction mitochondria base excision repair reactive oxygen species |
| title | Targeting Mitochondrial Function with Chemoptogenetics |
| title_full | Targeting Mitochondrial Function with Chemoptogenetics |
| title_fullStr | Targeting Mitochondrial Function with Chemoptogenetics |
| title_full_unstemmed | Targeting Mitochondrial Function with Chemoptogenetics |
| title_short | Targeting Mitochondrial Function with Chemoptogenetics |
| title_sort | targeting mitochondrial function with chemoptogenetics |
| topic | mitochondrial DNA chemoptogenetics mitochondrial dysfunction mitochondria base excision repair reactive oxygen species |
| url | https://www.mdpi.com/2227-9059/10/10/2459 |
| work_keys_str_mv | AT amyromesberg targetingmitochondrialfunctionwithchemoptogenetics AT bennettvanhouten targetingmitochondrialfunctionwithchemoptogenetics |