Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis

Witzig, Melissa and Grimm, Amandine and Schmitt, Karen and Lejri, Imane and Frank, Stephan and Brown, Steven A. and Eckert, Anne. (2020) Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis. Cells, 9 (10). p. 2323.

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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.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Neuroscience (Papassotiropoulos)
UniBasel Contributors:Grimm, Amandine and Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Sep 2021 14:16
Deposited On:23 Sep 2021 14:16

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