Table 1 Functions of cuproptosis-related genes
From: Cuproptosis in cancer: biological implications and therapeutic opportunities
Gene | Role in cuproptosis | Subcellular locations | Function description | References |
|---|---|---|---|---|
FDX1 | Reduce Cu2+ to Cu+; upstream regulatory factors of LA pathway; deletion attenuates cuproptosis | Mitochondrion matrix | Reduce Cu2+ to Cu+; regulate steroid hormone synthesis as electron transfer intermediates for mitochondrial cytochrome P450 (CYP450) | |
LIAS | Downstream effector molecules of FDX1; involved in LA pathway | Mitochondrion | Catalyze the conversion of octanoylated domains into lipoylated derivatives | |
LIPT1 | Downstream effector of FDX1; involved in LA pathway | Mitochondrion | Catalyze the transfer of a lipoyl group to the lysine residue of targeted enzymes | |
DLAT | Lipoylation and Cu+ binding lead to DLAT oligomerization and further result in cell death | Mitochondrion matrix | Catalyze the breakdown of pyruvate into acetyl-CoA as the E2 subunit of PDC complex | |
DLD | Not described | Mitochondrion and nucleus | The E3 subunit of PDC complex | |
PDHA1 | Not described | Mitochondrion matrix | Catalyze the conversion of pyruvate to acetyl-CoA as the E1 subunit A1 of PDC complex | |
PDHB | Not described | Mitochondrion matrix | Catalyze the conversion of pyruvate to acetyl-CoA as the E1 subunit B of PDC complex | |
MTF1 | Deletion results in increased sensitivity to cuproptosis | Cytoplasm and nucleus | Active the transcription of metallothionein and other genes involved in the homeostasis of heavy metals | |
GLS | Deletion results in increased sensitivity to cuproptosis | Cytoplasm and mitochondrion | Catalyze the breakdown of glutamine into glutamate | |
CDKN2A | Deletion results in increased sensitivity to cuproptosis | Cytoplasm and nucleus | Arrest the cell cycle in the G1 phase and G2 phase by forming complexes with CDK4/6, and cyclin D | |
ATP7A/B | Loss of function results in intracellular copper accumulation | Cell membrane, TGN membrane, and plasma membrane | Copper-transporting P-type ATPases | |
SLC31A1 | Overactivation results in intracellular copper accumulation | Cell membrane | Promote copper uptake as a high-affinity copper transporter | [69] |