Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts
Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/884 |
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| author | Kerstin Kuffner Julian Triebelhorn Katrin Meindl Christoph Benner André Manook Daniel Sudria-Lopez Ramona Siebert Caroline Nothdurfter Thomas C. Baghai Konstantin Drexler Mark Berneburg Rainer Rupprecht Vladimir M. Milenkovic Christian H. Wetzel |
| author_facet | Kerstin Kuffner Julian Triebelhorn Katrin Meindl Christoph Benner André Manook Daniel Sudria-Lopez Ramona Siebert Caroline Nothdurfter Thomas C. Baghai Konstantin Drexler Mark Berneburg Rainer Rupprecht Vladimir M. Milenkovic Christian H. Wetzel |
| author_sort | Kerstin Kuffner |
| collection | DOAJ |
| description | Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and adenosine triphosphate (ATP)-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance, which is associated with the molecular pathophysiology of MDD. The observed alterations in the oxidative phosphorylation system (OXPHOS) and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways. |
| first_indexed | 2024-03-10T20:40:45Z |
| format | Article |
| id | doaj.art-24acd33b68dd4aeca5c8514df4755758 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:40:45Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-24acd33b68dd4aeca5c8514df47557582023-11-19T20:41:07ZengMDPI AGCells2073-44092020-04-019488410.3390/cells9040884Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin FibroblastsKerstin Kuffner0Julian Triebelhorn1Katrin Meindl2Christoph Benner3André Manook4Daniel Sudria-Lopez5Ramona Siebert6Caroline Nothdurfter7Thomas C. Baghai8Konstantin Drexler9Mark Berneburg10Rainer Rupprecht11Vladimir M. Milenkovic12Christian H. Wetzel13Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Dermatology, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Dermatology, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, GermanyMitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and adenosine triphosphate (ATP)-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance, which is associated with the molecular pathophysiology of MDD. The observed alterations in the oxidative phosphorylation system (OXPHOS) and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.https://www.mdpi.com/2073-4409/9/4/884major depressionskin fibroblastsmitochondriabioenergeticsoxidative phosphorylationadenosine triphosphate |
| spellingShingle | Kerstin Kuffner Julian Triebelhorn Katrin Meindl Christoph Benner André Manook Daniel Sudria-Lopez Ramona Siebert Caroline Nothdurfter Thomas C. Baghai Konstantin Drexler Mark Berneburg Rainer Rupprecht Vladimir M. Milenkovic Christian H. Wetzel Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts Cells major depression skin fibroblasts mitochondria bioenergetics oxidative phosphorylation adenosine triphosphate |
| title | Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts |
| title_full | Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts |
| title_fullStr | Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts |
| title_full_unstemmed | Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts |
| title_short | Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts |
| title_sort | major depressive disorder is associated with impaired mitochondrial function in skin fibroblasts |
| topic | major depression skin fibroblasts mitochondria bioenergetics oxidative phosphorylation adenosine triphosphate |
| url | https://www.mdpi.com/2073-4409/9/4/884 |
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