Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis
| Autor: | Steven A. Brown, Anne Eckert, Amandine Grimm, Stephan Frank, Imane Lejri, Karen Schmitt, Melissa Witzig |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Neuroactive steroid
Circadian clock Mitochondrion Neuroprotection Models Biological Article 03 medical and health sciences Mice 0302 clinical medicine Receptors GABA Biological Clocks Cell Line Tumor circadian clock medicine Translocator protein Animals Humans Circadian rhythm lcsh:QH301-705.5 030304 developmental biology pregnenolone 0303 health sciences biology Chemistry General Medicine mitochondrial dynamics Cell biology Circadian Rhythm Mitochondria mitochondrial fusion lcsh:Biology (General) Pregnenolone biology.protein neurosteroid 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cells, Vol 9, Iss 2323, p 2323 (2020) Cells Volume 9 Issue 10 |
| ISSN: | 2073-4409 |
| Popis: | Neurosteroids are steroids synthetized in the nervous system, with the first step of steroidogenesis taking place within mitochondria with the synthesis of pregnenolone. They exert important brain-specific functions by playing a role in neurotransmission, learning and memory processes, and neuroprotection. Here, we show for the first time that mitochondrial neurosteroidogenesis follows a circadian rhythm and correlates with the rhythmic changes in mitochondrial morphology. We used synchronized human A172 glioma cells, which are steroidogenic cells with a functional core molecular clock, to show that pregnenolone levels and translocator protein (TSPO) are controlled by the clock, probably via circadian regulation of mitochondrial fusion/fission. Key findings were recapitulated in mouse brains. We also showed that genetic or pharmacological abrogation of fusion/fission activity, as well as disturbing the core molecular clock, abolished circadian rhythms of pregnenolone and TSPO. Our findings provide new insights into the crosstalk between mitochondrial function (here, neurosteroidogenesis) and circadian cycles. |
| Databáze: | OpenAIRE |
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