Enhancement of Intracellular Accumulation of Copper by Biogenesis of Lipid Droplets in Saccharomyces cerevisiae Revealed by Transcriptomic Analysis

Abstract

Copper is an essential micronutrient for life, whose homeostasis is rigorously regulated to meet the demands of normal biological processes and to minimize the potential toxicity. Copper enriched by yeast is regarded as a safe and bioavailable form of copper supplements. Here, a Saccharomyces cerevisiae mutant strain H247 with expanded storage capability of copper was obtained through atmospheric and room-temperature plasma treatment. Transcriptomic analyses found that transcriptional upregulation of DGA1 might be the major contributor to the enhancement of intracellular copper accumulation in strain H247. The positive correlation between biogenesis of lipid droplets and intracellular accumulation of copper was confirmed by overexpression of the diacylglycerol acyltransferase encoding genes DGA1 and LRO1 or knockout of DGA1. Lipid droplets are not only the storage pool of copper but might prompt the copper trafficking to mitochondria, vacuoles, and Golgi apparatus. These results provide new insights into the sophisticated copper homeostatic mechanisms and the biological functions of lipid droplets.

Adaptation of Proteome and Metabolism in Different Haplotypes of Rhodosporidium toruloides during Cu(I) and Cu(II) Stress

“…The presence of copper ions enhanced lipid droplet accumulation in S. cerevisiae , indicating a positive correlation between lipid droplet biogenesis and accumulation of copper ions, as lipid droplets could provide storage pools for these compounds. Furthermore, the droplets might enhance the trafficking of copper to compartments such as mitochondria, vacuoles, and the Golgi apparatus [ 16 ]. The exposure to sublethal amounts of Cu(II) induced oxidative stress comparable to stress induced by ROS in S. cerevisiae [ 32 ].…”

“…As stated earlier, copper ions are stored in organelles in S. cerevisiae to avoid excessive accumulation [ 16 ]. About 25% of copper ions were stored in lipid droplets, with vacuoles and mitochondria also representing major storage compartments.…”

“…Additionally, mitochondria and the Golgi apparatus are labile intracellular copper pools, which allow the cell to maintain the rapid kinetics of copper uptake and release [ 52 ]. Lipid droplets might facilitate the transport of copper ions as they interact with the Golgi apparatus, mitochondria, and vacuoles through physical contact as well as proteins present on their surface [ 16 ]. A new class of perilipin proteins was discovered in R. toruloides NP11, the expression of which correlates with lipid quantity, indicating their importance in lipid accumulation [ 53 ].…”

“…Moreover, intracellular homeostasis is tightly regulated in order to balance the cells’ demand for copper while simultaneously avoiding excessive accumulation. In Saccharomyces cerevisiae , it was demonstrated that vacuoles and mitochondria are the major compartments of storage for this element [ 16 ]. It was also hypothesized that vesicles as well as lipid droplets, through their capacity to bind heavy metals to a variety of proteins, organic acids and bases, or other molecules, could be involved in the intracellular storage and transport of copper ions [ 16 , 17 ].…”

“…In Saccharomyces cerevisiae , it was demonstrated that vacuoles and mitochondria are the major compartments of storage for this element [ 16 ]. It was also hypothesized that vesicles as well as lipid droplets, through their capacity to bind heavy metals to a variety of proteins, organic acids and bases, or other molecules, could be involved in the intracellular storage and transport of copper ions [ 16 , 17 ]. Free copper is able to subject cells to lethal amounts of oxidative stress, resulting in strong biotoxic effects, thereby damaging proteins, nucleic acids, and lipids or inhibiting enzymatic activity [ 15 , 18 , 19 ].…”