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Knockdown of the neuronal gene Lim3 at the early stages of development affects mitochondrial function and lifespan in Drosophilaстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 22 августа 2019 г.
- Авторы: Rybina Olga Y., Schelkunov Mikhail I., Veselkina Ekaterina R., Sarantseva Svetlana V., Krementsova Anna V., Vysokikh Mikhail Y., Melentev Pavel A., Volodina Maria A., Pasyukova Elena G.
- Журнал: Mechanisms of Ageing and Development
- Том: 181
- Год издания: 2019
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 29
- Последняя страница: 41
- DOI: 10.1016/j.mad.2019.111121
- Аннотация: 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.
- Добавил в систему: Высоких Михаил Юрьевич