Transcriptomic Insights into the Effect of Melatonin in Saccharomyces cerevisiae in the Presence and Absence of Oxidative Stress

Abstract

Melatonin is a ubiquitous indolamine that plays important roles in various aspects of biological processes in mammals. In Saccharomyces cerevisiae, melatonin has been reported to exhibit antioxidant properties and to modulate the expression of some genes involved in endogenous defense systems. The aim of this study was to elucidate the role of supplemented melatonin at the transcriptional level in S. cerevisiae in the presence and absence of oxidative stress. This was achieved by exposing yeast cells pretreated with different melatonin concentrations to hydrogen peroxide and assessing the entry of melatonin into the cell and the yeast response at the transcriptional level (by microarray and qPCR analyses) and the physiological level (by analyzing changes in the lipid composition and mitochondrial activity). We found that exogenous melatonin crossed cellular membranes at nanomolar concentrations and modulated the expression of many genes, mainly downregulating the expression of mitochondrial genes in the absence of oxidative stress, triggering a hypoxia-like response, and upregulating them under stress, mainly the cytochrome complex and electron transport chain. Other categories that were enriched by the effect of melatonin were related to transport, antioxidant activity, signaling, and carbohydrate and lipid metabolism. The overall results suggest that melatonin is able to reprogram the cellular machinery to achieve tolerance to oxidative stress.

Crosstalk between Peroxisomal Activities and Nrf2 Signaling in Porcine Embryos

“…PPARγ is also involved in peroxisomal biogenesis [ 54 ] and mediates embryo implantation and survival [ 55 ]. Sunyer-Figueres et al stated that Pex19 is regulated by melatonin, implying that melatonin can mediate FA β-oxidation in peroxisomes by Pex19 regulation [ 31 ]. This was corroborated by our finding that the content of FAs in the Cnd3-injected group was significantly lower than that in the control and melatonin/PA-treated groups ( Figure 7 b’).…”

“…This collaboration is known to participate in the categorization of membrane proteins for transportation to other organelles, such as lipid droplets and mitochondria [ 30 ]. Sunyer-Figueres et al reported that melatonin significantly increased the expression of Pex19, suggesting that melatonin upregulates β-oxidation of FAs in peroxisomes through the regulation of Pex19 [ 31 ]. Here, some studies raised an interesting suggestion that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway not only plays a role in the maintenance of cellular redox homeostasis, but also mediates the β-oxidation of FAs, mitochondrial membrane potential (MMP), and the production of ATP.…”

An Examination of the Putative Role of Melatonin in Exosome Biogenesis

“…A quantitative analysis of multiples genes related to different signaling transduction pathways in Saccharomyces cerevisiae under oxidative stress revealed mild to moderate expression of 29 genes regulating transmembrane transport activity after treatment with melatonin ( Sunyer-Figueres et al, 2020 ). It may be that whether and how simultaneous activation of MT1 and 2 influence exosome delivery is determined by the physiological state of the host cell.…”

“…It may be that whether and how simultaneous activation of MT1 and 2 influence exosome delivery is determined by the physiological state of the host cell. In addition to the molecular pathways that participate in exosome release, other findings indicate changes in the physicochemical properties of the cell membrane as a result of melatonin exposure ( Sunyer-Figueres et al, 2020 ). The report claimed a moderate rise in the synthesis of unsaturated fatty acids and sphingolipids upon treatment with melatonin, indicating an increase in membrane flexibility and fluidity ( Sunyer-Figueres et al, 2020 ).…”

“…In addition to the molecular pathways that participate in exosome release, other findings indicate changes in the physicochemical properties of the cell membrane as a result of melatonin exposure ( Sunyer-Figueres et al, 2020 ). The report claimed a moderate rise in the synthesis of unsaturated fatty acids and sphingolipids upon treatment with melatonin, indicating an increase in membrane flexibility and fluidity ( Sunyer-Figueres et al, 2020 ). In our previous work, we found that melatonin can alter the unsaturated/saturated fatty acid ratio by increasing Arachidonic acid, Oleic acid, and Linoleic acid levels and change the flexibility of the cell membrane, leading to enhanced exosome delivery ( Pournaghi et al, 2021 ).…”