The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species
Mitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (pro...
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2025-03-01
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| author | Yuki Kageyama Shohei Okura Ayaka Sukigara Ayaka Matsunaga Kunio Maekubo Takafumi Oue Koki Ishihara Yasuhiko Deguchi Koki Inoue |
| author_facet | Yuki Kageyama Shohei Okura Ayaka Sukigara Ayaka Matsunaga Kunio Maekubo Takafumi Oue Koki Ishihara Yasuhiko Deguchi Koki Inoue |
| author_sort | Yuki Kageyama |
| collection | DOAJ |
| description | Mitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing cell metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) and mitochondrial dysfunction. Mitochondrial dysfunction contributes to oxidative stress, particularly through the generation of ROS, which are implicated in the pathophysiology of BD. Oxidative stress arises when there is an imbalance between the production of ROS and the cell’s ability to neutralize them. In neurons, excessive ROS can damage various cellular components, including proteins in neuronal membranes and intracellular enzymes. Such damage may interfere with neurotransmitter reuptake and the function of critical enzymes, potentially affecting brain regions involved in mood regulation and emotional control, which are key aspects of BD. In this review, we will explore how various types of mitochondrial dysfunction contribute to the production of ROS. These include disruptions in energy metabolism, impaired ROS management, and defects in mitochondrial quality control mechanisms such as mitophagy (the process by which damaged mitochondria are selectively degraded). We will also examine how abnormalities in calcium signaling, which is crucial for synaptic plasticity, can lead to mitochondrial dysfunction. Additionally, we will discuss the specific mitochondrial dysfunctions observed in BD, highlighting how these defects may contribute to the disorder’s pathophysiology. Finally, we will identify potential therapeutic targets to improve mitochondrial function, which could pave the way for new treatments to manage or mitigate symptoms of BD. |
| format | Article |
| id | doaj-art-9075bac4d9c349bf97091eb9e9b362cf |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-9075bac4d9c349bf97091eb9e9b362cf2025-08-20T03:43:30ZengMDPI AGBiomolecules2218-273X2025-03-0115338310.3390/biom15030383The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen SpeciesYuki Kageyama0Shohei Okura1Ayaka Sukigara2Ayaka Matsunaga3Kunio Maekubo4Takafumi Oue5Koki Ishihara6Yasuhiko Deguchi7Koki Inoue8Department of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neuropsychiatry, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, JapanMitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing cell metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) and mitochondrial dysfunction. Mitochondrial dysfunction contributes to oxidative stress, particularly through the generation of ROS, which are implicated in the pathophysiology of BD. Oxidative stress arises when there is an imbalance between the production of ROS and the cell’s ability to neutralize them. In neurons, excessive ROS can damage various cellular components, including proteins in neuronal membranes and intracellular enzymes. Such damage may interfere with neurotransmitter reuptake and the function of critical enzymes, potentially affecting brain regions involved in mood regulation and emotional control, which are key aspects of BD. In this review, we will explore how various types of mitochondrial dysfunction contribute to the production of ROS. These include disruptions in energy metabolism, impaired ROS management, and defects in mitochondrial quality control mechanisms such as mitophagy (the process by which damaged mitochondria are selectively degraded). We will also examine how abnormalities in calcium signaling, which is crucial for synaptic plasticity, can lead to mitochondrial dysfunction. Additionally, we will discuss the specific mitochondrial dysfunctions observed in BD, highlighting how these defects may contribute to the disorder’s pathophysiology. Finally, we will identify potential therapeutic targets to improve mitochondrial function, which could pave the way for new treatments to manage or mitigate symptoms of BD.https://www.mdpi.com/2218-273X/15/3/383bipolar disorderinflammationmitophagysynaptic plasticityreactive oxygen species |
| spellingShingle | Yuki Kageyama Shohei Okura Ayaka Sukigara Ayaka Matsunaga Kunio Maekubo Takafumi Oue Koki Ishihara Yasuhiko Deguchi Koki Inoue The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species Biomolecules bipolar disorder inflammation mitophagy synaptic plasticity reactive oxygen species |
| title | The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species |
| title_full | The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species |
| title_fullStr | The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species |
| title_full_unstemmed | The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species |
| title_short | The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species |
| title_sort | association among bipolar disorder mitochondrial dysfunction and reactive oxygen species |
| topic | bipolar disorder inflammation mitophagy synaptic plasticity reactive oxygen species |
| url | https://www.mdpi.com/2218-273X/15/3/383 |
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