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Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis
- Source :
- Cells, Vol 9, Iss 2323, p 2323 (2020), Cells, Volume 9, Issue 10
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 9
- Issue :
- 2323
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....3b61958336fd014a734b77258710b661