Adrenal Dysfunction in Mitochondrial Diseases
Cortisol is central to several homeostatic mechanisms including the stress and immune response. Adrenal insufficiency and impaired cortisol production leads to severe, potentially fatal disorders. Several fundamental stages of steroidogenesis occur within the mitochondria. These dynamic organelles n...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/2/1126 |
| _version_ | 1797441525769043968 |
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| author | Madeleine Corkery-Hayward Louise A. Metherell |
| author_facet | Madeleine Corkery-Hayward Louise A. Metherell |
| author_sort | Madeleine Corkery-Hayward |
| collection | DOAJ |
| description | Cortisol is central to several homeostatic mechanisms including the stress and immune response. Adrenal insufficiency and impaired cortisol production leads to severe, potentially fatal disorders. Several fundamental stages of steroidogenesis occur within the mitochondria. These dynamic organelles not only contribute ATP for steroidogenesis, but also detoxify harmful by-products generated during cortisol synthesis (reactive oxygen species). Mutations in nuclear or mitochondrial DNA that impair mitochondrial function lead to debilitating multi-system diseases. Recently, genetic variants that impair mitochondrial function have been identified in people with isolated cortisol insufficiency. This review aimed to clarify the association between mitochondrial diseases and adrenal insufficiency to produce cortisol. Mitochondrial diseases are rare and mitochondrial diseases that feature adrenal insufficiency are even rarer. We identified only 14 cases of adrenal insufficiency in people with confirmed mitochondrial diseases globally. In line with previous reviews, adrenal dysfunction was most prevalent in mitochondrial deletion syndromes (particularly Pearson syndrome and Kearns–Sayre syndrome) and with point mutations that compromised oxidative phosphorylation. Although adrenal insufficiency has been reported with mitochondrial diseases, the incidence reflects that expected in the general population. Thus, it is unlikely that mitochondrial mutations alone are responsible for an insufficiency to produce cortisol. More research is needed into the pathogenesis of adrenal disease in these individuals. |
| first_indexed | 2024-03-09T12:25:23Z |
| format | Article |
| id | doaj.art-01bf044067c142a9abd211209c1d88fe |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:25:23Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-01bf044067c142a9abd211209c1d88fe2023-11-30T22:35:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242112610.3390/ijms24021126Adrenal Dysfunction in Mitochondrial DiseasesMadeleine Corkery-Hayward0Louise A. Metherell1Barts and the London Medical School, Queen Mary University of London, London E1 2AD, UKCentre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UKCortisol is central to several homeostatic mechanisms including the stress and immune response. Adrenal insufficiency and impaired cortisol production leads to severe, potentially fatal disorders. Several fundamental stages of steroidogenesis occur within the mitochondria. These dynamic organelles not only contribute ATP for steroidogenesis, but also detoxify harmful by-products generated during cortisol synthesis (reactive oxygen species). Mutations in nuclear or mitochondrial DNA that impair mitochondrial function lead to debilitating multi-system diseases. Recently, genetic variants that impair mitochondrial function have been identified in people with isolated cortisol insufficiency. This review aimed to clarify the association between mitochondrial diseases and adrenal insufficiency to produce cortisol. Mitochondrial diseases are rare and mitochondrial diseases that feature adrenal insufficiency are even rarer. We identified only 14 cases of adrenal insufficiency in people with confirmed mitochondrial diseases globally. In line with previous reviews, adrenal dysfunction was most prevalent in mitochondrial deletion syndromes (particularly Pearson syndrome and Kearns–Sayre syndrome) and with point mutations that compromised oxidative phosphorylation. Although adrenal insufficiency has been reported with mitochondrial diseases, the incidence reflects that expected in the general population. Thus, it is unlikely that mitochondrial mutations alone are responsible for an insufficiency to produce cortisol. More research is needed into the pathogenesis of adrenal disease in these individuals.https://www.mdpi.com/1422-0067/24/2/1126adrenal insufficiencymitochondriafamilial glucocorticoid deficiencymitochondrial diseases |
| spellingShingle | Madeleine Corkery-Hayward Louise A. Metherell Adrenal Dysfunction in Mitochondrial Diseases International Journal of Molecular Sciences adrenal insufficiency mitochondria familial glucocorticoid deficiency mitochondrial diseases |
| title | Adrenal Dysfunction in Mitochondrial Diseases |
| title_full | Adrenal Dysfunction in Mitochondrial Diseases |
| title_fullStr | Adrenal Dysfunction in Mitochondrial Diseases |
| title_full_unstemmed | Adrenal Dysfunction in Mitochondrial Diseases |
| title_short | Adrenal Dysfunction in Mitochondrial Diseases |
| title_sort | adrenal dysfunction in mitochondrial diseases |
| topic | adrenal insufficiency mitochondria familial glucocorticoid deficiency mitochondrial diseases |
| url | https://www.mdpi.com/1422-0067/24/2/1126 |
| work_keys_str_mv | AT madeleinecorkeryhayward adrenaldysfunctioninmitochondrialdiseases AT louiseametherell adrenaldysfunctioninmitochondrialdiseases |