Low Ctr1p, due to lack of Sco1p results in lowered cisplatin uptake and mediates insensitivity of rho0 yeast to cisplatin

Bodiga, Sreedhar; Vemuri, Praveen Kumar; Bodiga, Vijaya Lakshmi

doi:10.1016/j.jinorgbio.2018.07.003

Cited by 7 publications

(2 citation statements)

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“…Cisplatin can enter the cells by passive diffusion but recently a lot of interest has been given to active uptake of the drug. In particular, for the transport of cisplatin into the cells via facilitated diffusion, the copper transporter proteins (CTR1 and CTR2) seem to be involved in the uptake of the drug [17,18]. Once inside the cell, the activation of CDDP is due to the different chloride concentration between blood plasma (~100 mM) and cell cytoplasm (~4 mM).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Involvement in Cisplatin Resistance

Cocetta

Ragazzi

Montopoli

2019

IJMS

107

102

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Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Involvement in Cisplatin Resistance

Cocetta

Ragazzi

Montopoli

2019

IJMS

107

102

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“…cerevisiae have been investigated by several groups. ,, The divalent copper ions in extracellular solution are reduced to univalent copper ions by cupric reductase (Fre1p and Fre2p) on the cell membrane and then imported to the cytoplasm by high-affinity copper transporters (Ctr proteins, such as Ctr1p and Ctr3p) or low-affinity transporters such as Smf1p and Fet4p. − The intracellular copper ions can be delivered to its appropriate and specific destinations including organelles and cuproproteins via various copper chaperones and buffering components to facilitate the storage of copper or drive copper-dependent biochemical processes. ,, The intracellular homeostasis of copper is tightly regulated to balance the cellular demands and the putative toxicity resulting from excessive accumulation of copper. Vacuoles and mitochondria are regarded as the major compartments for copper storage to avoid toxicity. − A certain relationship between copper metabolism and cisplatin metabolism has been reported. − Cisplatin causes degradation and delocalization of Ctr1p and interferes with copper uptake in yeast cells . Moreover, cisplatin cytotoxicity is potentiated at copper deprivation due to lowered antioxidant defense and increased oxidative stress .…”

Section: Introductionmentioning

confidence: 99%

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

Guo

et al. 2022

J. Agric. Food Chem.

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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.

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