Copper metabolism in Saccharomyces cerevisiae: an update.

Affiliation

Shi H(1)(2), Jiang Y(3), Yang Y(4)(5), Peng Y(6), Li C(7).
Author information:
(1)Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China.
(2)Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
(3)Pathology Department, The Second People's Hospital of Jingmen, Jingmen, 448000, China.
(4)Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
(5)West China School of Nursing, Sichuan University, Chengdu, 610041, Sichuan, China.
(6)Department of General Surgery, The Second People's Hospital of Jingmen, Jingmen, 448000, China.
(7)Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China. [Email]

Abstract

Copper is an essential element in all forms of life. It acts as a cofactor of some enzymes and is involved in forming proper protein conformations. However, excess copper ions in cells are detrimental as they can generate free radicals or disrupt protein structures. Therefore, all life forms have evolved conserved and exquisite copper metabolic systems to maintain copper homeostasis. The yeast Saccharomyces cerevisiae has been widely used to investigate copper metabolism as it is convenient for this purpose. In this review, we summarize the mechanism of copper metabolism in Saccharomyces cerevisiae according to the latest literature. In brief, bioavailable copper ions are incorporated into yeast cells mainly via the high-affinity transporters Ctr1 and Ctr3. Then, intracellular Cu+ ions are delivered to different organelles or cuproproteins by different chaperones, including Ccs1, Atx1, and Cox17. Excess copper ions bind to glutathione (GSH), metallothioneins, and copper complexes are sequestered into vacuoles to avoid toxicity. Copper-sensing transcription factors Ace1 and Mac1 regulate the expression of genes involved in copper detoxification and uptake/mobilization in response to changes in intracellular copper levels. Though numerous recent breakthroughs in understanding yeast's copper metabolism have been achieved, some issues remain unresolved. Completely elucidating the mechanism of copper metabolism in yeast helps decode the corresponding system in humans and understand how copper-related diseases develop.