Mitochondrial inhibitors reveal roles of specific respiratory chain complexes in CRY-dependent degradation of TIM.
Circadian clock
Cryptochrome
Mitochondria
Respiratory chain
Timeless
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
20
05
2024
accepted:
24
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Drosophila Cryptochrome (CRY) is an essential photoreceptor that mediates the resetting of the circadian clock by light. in vitro studies demonstrated a critical role of redox cycling of the FAD cofactor for CRY activation by light. However, it is unknown if CRY responds to cellular redox environment to modulate the circadian clock. We report here that the mitochondrial respiratory chain impinges on CRY activity. Inhibition of complex III and V blocks CRY-mediated degradation of TIMELESS (TIM) in response to light, and also blocks light-induced CRY degradation. On the other hand, inhibition of complex I facilitates TIM degradation even in the dark. Mutations of critical residues of the CRY C-terminus promote TIM degradation in the dark, even in the presence of complex III and V inhibitors. We propose that complex III and V activities are important for activation of CRY in response to light. Interestingly, we found that transcriptional repressor functions of Drosophila and mammalian CRY proteins are not affected by mitochondrial inhibitors. Together these data suggest that the two functions of CRY have different sensitivity to disruptions of the mitochondrial respiratory chain: one is sensitive to mitochondrial activities that enable resetting, the other is insensitive so as to sustain the molecular oscillator.
Identifiants
pubmed: 39472713
doi: 10.1038/s41598-024-77692-0
pii: 10.1038/s41598-024-77692-0
doi:
Substances chimiques
Cryptochromes
0
Drosophila Proteins
0
tim protein, Drosophila
0
cry protein, Drosophila
0
Electron Transport Complex III
EC 7.1.1.8
Eye Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26051Subventions
Organisme : NINDS NIH HHS
ID : 5R37NS048471
Pays : United States
Organisme : NIGMS NIH HHS
ID : 2R15GM109282-03
Pays : United States
Informations de copyright
© 2024. The Author(s).
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