Widespread post-transcriptional regulation of co-transmission

Chen, Nannan; Zhang, Yunpeng; Rivera-Rodriguez, Emmanuel J.; Yu, Albert D.; Hobin, Michael; Rosbash, Michael; Griffith, Leslie C.

doi:10.1101/2023.03.01.530653

Cited by 2 publications

(2 citation statements)

References 34 publications

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“…1d); some also transcribed the gene encoding the vesicular acetylcholine transporter VAChT (Supplementary Fig. 1d)—a common occurrence in non-cholinergic neurons, which rely on a microRNA to suppress its translation 14 .…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial origins of the pressure to sleep

Sarnataro,

Velasco,

Monaco

et al. 2024

Preprint

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SummaryThe neural control of sleep requires that sleep need is sensed during waking and discharged during sleep. To obtain a comprehensive, unbiased view of molecular changes in the brain that may underpin these processes, we have characterized the transcriptomes of single cells isolated from rested and sleep-deprived flies. Transcripts upregulated after sleep deprivation, in sleep-control neurons projecting to the dorsal fan-shaped body (dFBNs) but not ubiquitously in the brain, encode almost exclusively proteins with roles in mitochondrial respiration and ATP synthesis. These gene expression changes are accompanied by mitochondrial fragmentation, enhanced mitophagy, and an increase in the number of contacts between mitochondria and the endoplasmic reticulum, creating conduits for the replenishment of peroxidized lipids. The morphological changes are reversible after recovery sleep and blunted by the installation of an electron overflow in the respiratory chain. Inducing or preventing mitochondrial fission or fusion in dFBNs alters sleep and the electrical properties of sleep-control cells in opposite directions: hyperfused mitochondria increase, whereas fragmented mitochondria decrease, neuronal excitability and sleep. ATP levels in dFBNs rise after enforced waking because of diminished ATP consumption during the arousal-mediated inhibition of these neurons, which predisposes them to heightened oxidative stress. Consistent with this view, uncoupling electron flux from ATP synthesis relieves the pressure to sleep, while exacerbating mismatches between electron supply and ATP demand (by powering ATP synthesis with a light-driven proton pump) promotes sleep. Sleep, like ageing, may be an inescapable consequence of aerobic metabolism.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial origins of the pressure to sleep

Sarnataro,

Velasco,

Monaco

et al. 2024

Preprint

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“…As in the mammalian brain, there is increasing recognition of neurotransmitter co-transmission in Drosophila, including in neurons that co-release DA alongside glutamate 36,70,[86][87][88][89][90][91] . In this study, we comprehensively mapped dVGLUT expression throughout the fly DA system for the first time.…”

Section: Discussionmentioning

confidence: 99%

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

Buck,

Rubin,

Kunkhyen

et al. 2023

Preprint

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SummaryParkinson’s disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 andDrosophilaortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1β as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.

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Widespread post-transcriptional regulation of co-transmission

Cited by 2 publications

References 34 publications

Mitochondrial origins of the pressure to sleep

Mitochondrial origins of the pressure to sleep

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

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