Knockdown of the neuronal gene Lim3 at the early stages of development affects mitochondrial function and lifespan in Drosophila
| Autor: | Elena G. Pasyukova, Maria A. Volodina, S. V. Sarantseva, Olga Y. Rybina, A. V. Krementsova, Ekaterina R. Veselkina, Pavel A. Melentev, Mikhail I. Schelkunov, Mikhail Vysokikh |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aging LIM-Homeodomain Proteins Longevity 03 medical and health sciences 0302 clinical medicine Transcription (biology) medicine Animals Drosophila Proteins Transcription factor Gene Gene knockdown biology biology.organism_classification Embryonic stem cell Cell biology Mitochondria 030104 developmental biology medicine.anatomical_structure Drosophila melanogaster Gene Knockdown Techniques Larva Neuron LHX3 Reactive Oxygen Species Oxidation-Reduction 030217 neurology & neurosurgery Developmental Biology Transcription Factors |
| Zdroj: | Mechanisms of ageing and development. 181 |
| ISSN: | 1872-6216 |
| Popis: | Understanding the molecular mechanisms underlying variation in lifespan is central to ensure long life. Lim3 encoding a homolog of the vertebrate Lhx3/4 transcription factors plays a key role in Drosophila neuron development. Here, we demonstrated that Lim3 knockdown early in life decreased survival of adult flies. To study the mechanisms underlying this effect, we identified embryonic Lim3 targets using combined RNA-seq and RT-qPCR analyses complemented by in silico analysis of Lim3 binding sites. Though genes with neuronal functions were revealed as Lim3 targets, the characteristics of neurons were not affected by Lim3 depletion. Many of the direct and indirect Lim3 target genes were associated with mitochondrial function, ATP-related activity, redox processes and antioxidant defense. Consistent with the observed changes in the embryonic transcription of these genes, ROS levels were increased in embryos, which could cause changes in the transcription of indirect Lim3 targets known to affect lifespan. We hypothesize that altered mitochondrial activity is crucial for the decrease of adult lifespan caused by Lim3 knockdown early in life. In adults that encountered Lim3 depletion early in life, the transcription of several genes remained altered, and mitochondrial membrane potential, ATP level and locomotion were increased, confirming the existence of carry-over effects. |
| Databáze: | OpenAIRE |
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