A screen for iron metabolism genes that influence circadian rhythms implicates Ferritin 2 Light Chain Homologue in the Drosophila clock
Abstract
Heme has been previously implicated in the function of the mammalian circadian clock
but there has been no systematic investigation into the interplay between iron
homeostasis and circadian rhythms. I have addressed this question in the model
organism Drosophila melanogaster using two different approaches. First, I measured
the amount and iron content of the iron storage protein ferritin, the activity of the iron
sulfur cluster-containing enzyme aconitase and total heme content in whole bodies of
Drosophila at different times during the 24-hour day-night cycle. I found no apparent
fluctuation in these assays that would suggest circadian regulation of iron metabolism.
Second, I tested whether RNA interference (RNAi) of iron homeostasis genes would
alter the circadian behaviour of the flies. I selected 48 genes related to iron metabolism,
silenced their expression specifically in cells expressing the circadian time-keeping
transcription factor timeless and monitored the ability of these flies to sustain circadian
rhythms in the absence of light cues. I found that when one of the two ferritin subunits,
Ferritin 2 Light Chain Homologue (Fer2LCH) was silenced in clock cells the resulting
flies displayed disrupted circadian rhythms in constant darkness. Expression of the
circadian clock transcription factors timeless and period was disrupted in Fer2LCHRNAi
flies. Inducing RNAi in restricted subsets of neurons I observed defects when
Fer2LCH expression was reduced in the small ventral lateral neurons and in the dorsal
lateral neurons that express the photoreceptor cryptochrome. An enhancer trap in
Fer2LCH showed expression in a subset of these neurons. I propose a new role for
Fer2LCH in the function of the biological clock in Drosophila melanogaster.
Authors
Mandilaras, KonstantinosCollections
- Theses [4389]