Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease

The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabol...

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Main Authors: Iseline Cardon, Sonja Grobecker, Selin Kücükoktay, Stefanie Bader, Tatjana Jahner, Caroline Nothdurfter, Kevin Koschitzki, Mark Berneburg, Bernhard H. F. Weber, Heidi Stöhr, Marcus Höring, Gerhard Liebisch, Frank Braun, Tanja Rothammer-Hampl, Markus J. Riemenschneider, Rainer Rupprecht, Vladimir M. Milenkovic, Christian H. Wetzel
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/2/963
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author Iseline Cardon
Sonja Grobecker
Selin Kücükoktay
Stefanie Bader
Tatjana Jahner
Caroline Nothdurfter
Kevin Koschitzki
Mark Berneburg
Bernhard H. F. Weber
Heidi Stöhr
Marcus Höring
Gerhard Liebisch
Frank Braun
Tanja Rothammer-Hampl
Markus J. Riemenschneider
Rainer Rupprecht
Vladimir M. Milenkovic
Christian H. Wetzel
author_facet Iseline Cardon
Sonja Grobecker
Selin Kücükoktay
Stefanie Bader
Tatjana Jahner
Caroline Nothdurfter
Kevin Koschitzki
Mark Berneburg
Bernhard H. F. Weber
Heidi Stöhr
Marcus Höring
Gerhard Liebisch
Frank Braun
Tanja Rothammer-Hampl
Markus J. Riemenschneider
Rainer Rupprecht
Vladimir M. Milenkovic
Christian H. Wetzel
author_sort Iseline Cardon
collection DOAJ
description The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD’s pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient (“Non-R”) and another with an unexplained mitochondrial disorder (“Mito”). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient’s data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient’s data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD.
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spelling doaj.art-0dca2d547cd348c485b0ad25245fc6f32024-01-29T13:55:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125296310.3390/ijms25020963Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated DiseaseIseline Cardon0Sonja Grobecker1Selin Kücükoktay2Stefanie Bader3Tatjana Jahner4Caroline Nothdurfter5Kevin Koschitzki6Mark Berneburg7Bernhard H. F. Weber8Heidi Stöhr9Marcus Höring10Gerhard Liebisch11Frank Braun12Tanja Rothammer-Hampl13Markus J. Riemenschneider14Rainer Rupprecht15Vladimir M. Milenkovic16Christian H. Wetzel17Department 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, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Dermatology, Regensburg University Hospital, 93053 Regensburg, GermanyInstitute of Human Genetics, University of Regensburg, 93053 Regensburg, GermanyInstitute of Human Genetics, University of Regensburg, 93053 Regensburg, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, 93053 Regensburg, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Neuropathology, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Neuropathology, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Neuropathology, Regensburg University Hospital, 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, GermanyThe link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD’s pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient (“Non-R”) and another with an unexplained mitochondrial disorder (“Mito”). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient’s data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient’s data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD.https://www.mdpi.com/1422-0067/25/2/963major depressive disordermitochondrial functionsmitochondriopathytreatment-resistant depressioniPS-neuronsiPS-astrocytes
spellingShingle Iseline Cardon
Sonja Grobecker
Selin Kücükoktay
Stefanie Bader
Tatjana Jahner
Caroline Nothdurfter
Kevin Koschitzki
Mark Berneburg
Bernhard H. F. Weber
Heidi Stöhr
Marcus Höring
Gerhard Liebisch
Frank Braun
Tanja Rothammer-Hampl
Markus J. Riemenschneider
Rainer Rupprecht
Vladimir M. Milenkovic
Christian H. Wetzel
Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
International Journal of Molecular Sciences
major depressive disorder
mitochondrial functions
mitochondriopathy
treatment-resistant depression
iPS-neurons
iPS-astrocytes
title Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
title_full Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
title_fullStr Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
title_full_unstemmed Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
title_short Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease
title_sort mitochondrial and cellular function in fibroblasts induced neurons and astrocytes derived from case study patients insights into major depression as a mitochondria associated disease
topic major depressive disorder
mitochondrial functions
mitochondriopathy
treatment-resistant depression
iPS-neurons
iPS-astrocytes
url https://www.mdpi.com/1422-0067/25/2/963
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