Regulatory Relationship between the Keap1/Nrf2/ARE Signaling System and Transcriptional Regulators of Lysosomal Biogenesis

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Abstract

Despite the key role of the Keap1/Nrf2/ARE redox-sensitive signaling system in cellular metabolism, little is known about its relationship to lysosome biogenesis. In this paper, a theoretical and experimental analysis of the possibility of such a link has been carried out. By forming a position frequency matrix in the transcription factor genes TFEB and TFE3, the presence of a large number of ARE-like sequences was found in the non-coding regions. In vitro exposure to J774 cells by Keap1/Nrf2/ARE activators (original synthetic monophenol TS-13 and tert-butylhydroquinone as comparison compound) results in dose-dependent induction of Tfe3 and Tfeb genes, accompanied by a gradual increase in the lysosome number and autosomal-lysosomal fusion intensity. Thus, it can be assumed that the proteins controlling the ARE-dependent genes are able to influence lysosome biogenesis.

About the authors

A. V. Chechushkov

Federal Research Center for Fundamental and Translational Medicine

Email: lemen7383@mail.ru
Russia, 630117, Novosibirsk

E. B. Menshchikova

Federal Research Center for Fundamental and Translational Medicine

Author for correspondence.
Email: lemen7383@mail.ru
Russia, 630117, Novosibirsk

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