PGC-1α activity and mitochondrial dysfunction in preterm infants
Extremely low gestational age neonates (ELGANs) are born in a relatively hyperoxic environment with weak antioxidant defenses, placing them at high risk for mitochondrial dysfunction affecting multiple organ systems including the nervous, respiratory, ocular, and gastrointestinal systems. The brain...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.997619/full |
| _version_ | 1811258943906775040 |
|---|---|
| author | Atefeh Mohammadi Atefeh Mohammadi Randa Higazy Estelle B. Gauda Estelle B. Gauda |
| author_facet | Atefeh Mohammadi Atefeh Mohammadi Randa Higazy Estelle B. Gauda Estelle B. Gauda |
| author_sort | Atefeh Mohammadi |
| collection | DOAJ |
| description | Extremely low gestational age neonates (ELGANs) are born in a relatively hyperoxic environment with weak antioxidant defenses, placing them at high risk for mitochondrial dysfunction affecting multiple organ systems including the nervous, respiratory, ocular, and gastrointestinal systems. The brain and lungs are highly affected by mitochondrial dysfunction and dysregulation in the neonate, causing white matter injury (WMI) and bronchopulmonary dysplasia (BPD), respectively. Adequate mitochondrial function is important in providing sufficient energy for organ development as it relates to alveolarization and axonal myelination and decreasing oxidative stress via reactive oxygen species (ROS) and reactive nitrogen species (RNS) detoxification. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a master regulator of mitochondrial biogenesis and function. Since mitochondrial dysfunction is at the root of WMI and BPD pathobiology, exploring therapies that can regulate PGC-1α activity may be beneficial. This review article describes several promising therapeutic agents that can mitigate mitochondrial dysfunction through direct and indirect activation and upregulation of the PGC-1α pathway. Metformin, resveratrol, omega 3 fatty acids, montelukast, L-citrulline, and adiponectin are promising candidates that require further pre-clinical and clinical studies to understand their efficacy in decreasing the burden of disease from WMI and BPD in preterm infants. |
| first_indexed | 2024-04-12T18:22:07Z |
| format | Article |
| id | doaj.art-ea36ba13640341cf993c81f0b2d50b2e |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T18:22:07Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ea36ba13640341cf993c81f0b2d50b2e2022-12-22T03:21:24ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.997619997619PGC-1α activity and mitochondrial dysfunction in preterm infantsAtefeh Mohammadi0Atefeh Mohammadi1Randa Higazy2Estelle B. Gauda3Estelle B. Gauda4The Hospital for Sick Children, Division of Neonatology, Department of Pediatrics and Translational Medicine Program, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaThe Hospital for Sick Children, Division of Neonatology, Department of Pediatrics and Translational Medicine Program, Toronto, ON, CanadaThe Hospital for Sick Children, Division of Neonatology, Department of Pediatrics and Translational Medicine Program, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaExtremely low gestational age neonates (ELGANs) are born in a relatively hyperoxic environment with weak antioxidant defenses, placing them at high risk for mitochondrial dysfunction affecting multiple organ systems including the nervous, respiratory, ocular, and gastrointestinal systems. The brain and lungs are highly affected by mitochondrial dysfunction and dysregulation in the neonate, causing white matter injury (WMI) and bronchopulmonary dysplasia (BPD), respectively. Adequate mitochondrial function is important in providing sufficient energy for organ development as it relates to alveolarization and axonal myelination and decreasing oxidative stress via reactive oxygen species (ROS) and reactive nitrogen species (RNS) detoxification. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a master regulator of mitochondrial biogenesis and function. Since mitochondrial dysfunction is at the root of WMI and BPD pathobiology, exploring therapies that can regulate PGC-1α activity may be beneficial. This review article describes several promising therapeutic agents that can mitigate mitochondrial dysfunction through direct and indirect activation and upregulation of the PGC-1α pathway. Metformin, resveratrol, omega 3 fatty acids, montelukast, L-citrulline, and adiponectin are promising candidates that require further pre-clinical and clinical studies to understand their efficacy in decreasing the burden of disease from WMI and BPD in preterm infants.https://www.frontiersin.org/articles/10.3389/fphys.2022.997619/fullmitochondrial dysfunctionoxidative stressreactive oxygen speciesPGC-1αwhite matter injurybronchopulmonary dysplasia |
| spellingShingle | Atefeh Mohammadi Atefeh Mohammadi Randa Higazy Estelle B. Gauda Estelle B. Gauda PGC-1α activity and mitochondrial dysfunction in preterm infants Frontiers in Physiology mitochondrial dysfunction oxidative stress reactive oxygen species PGC-1α white matter injury bronchopulmonary dysplasia |
| title | PGC-1α activity and mitochondrial dysfunction in preterm infants |
| title_full | PGC-1α activity and mitochondrial dysfunction in preterm infants |
| title_fullStr | PGC-1α activity and mitochondrial dysfunction in preterm infants |
| title_full_unstemmed | PGC-1α activity and mitochondrial dysfunction in preterm infants |
| title_short | PGC-1α activity and mitochondrial dysfunction in preterm infants |
| title_sort | pgc 1α activity and mitochondrial dysfunction in preterm infants |
| topic | mitochondrial dysfunction oxidative stress reactive oxygen species PGC-1α white matter injury bronchopulmonary dysplasia |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.997619/full |
| work_keys_str_mv | AT atefehmohammadi pgc1aactivityandmitochondrialdysfunctioninpreterminfants AT atefehmohammadi pgc1aactivityandmitochondrialdysfunctioninpreterminfants AT randahigazy pgc1aactivityandmitochondrialdysfunctioninpreterminfants AT estellebgauda pgc1aactivityandmitochondrialdysfunctioninpreterminfants AT estellebgauda pgc1aactivityandmitochondrialdysfunctioninpreterminfants |