Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase

Plant Endomembrane Dynamics: Studies of K+/H+ Antiporters Provide Insights on the Effects of pH and Ion Homeostasis

“…Notably, both participate in pH homeostasis: AtNHX1 restores growth at acidic pH, whereas AtCHX17 is effective at alkaline pH. These results are mimicked by yeast ScNhx1 and ScKha1, which promote growth best at pH 5 (Nass et al, 1997) and at weak alkaline pH (Wu et al, 2016), respectively.…”

“…Several genes involved in metal homeostasis are important for yeast survival on alkaline medium (Serrano et al, 2004). Recently Sckha1 was identified in a screen for mutants unable to grow on medium depleted of Cu (Wu et al, 2016). The kha1 mutant had reduced Fe levels and reduced Fet3 ferroxidase activity, although Cu levels were unchanged.…”

Iron Regulatory Mechanisms in Saccharomyces cerevisiae

“…(3) the vacuolar mobilization machinery constituted by the Fre6 metalloreductase, and the Fet5/Fth1 (paralogs of Fet3/Ftr1) and Smf3 iron exporters; (4) iron recycling proteins such as the Hmx1 heme oxygenase; (5) mitochondrial iron importers including Mrs4; (6) iron-independent alternatives to iron-using processes such as the biotin and 7-keto-8-aminopelargonic acid (KAPA) importers Vht1 and Bio5, respectively; and (7) the mRNAbinding proteins Cth1 and Cth2 implicated in iron metabolism remodeling (Figure 1). Recent studies have identified novel genes activated by Aft1 in response to iron depletion: (1) the trans-Golgi network K + /H + -exchanger gene KHA1, which product facilitates copper loading into apo-Fet3 multicopper-ferroxidase (Wu et al, 2016); (2) MMT1 and MMT2 mitochondrial iron exporter genes (Li et al, 2020); (3) RNR1, encoding for the catalytic subunit of the iron-dependent ribonucleotide reductase (RNR) enzyme; and (4) RNR1 transcriptional activator IXR1 (Ros-Carrero et al, 2020).…”

Is copper a new target to counteract the progression of chronic diseases?

“…Cu is a key element for a wide range of physiological cellular functions: aerobic respiration, oxidative stress protection, cardiovascular functionality, neuropeptide biogenesis, lipid, iron and potassium metabolism, erythropoiesis and angiogenesis. [1][2][3][4][5][6] Cu in metabolic processes is associated with its ability to fluctuate between oxidized (Cu 2+ ) and reduced (Cu + ) states, as a result of accepting and donating single electrons in oxido-reductive cellular reactions. 7 Thus, Cu is essential as a structural component for different proteins, as well as a catalytic cofactor for the activation of several metallo-enzymes, such as superoxide dismutase (SOD) and cytochrome c oxidase (or mitochondrial complex IV), 8,9 as seen in Fig.…”