Table 4 Ferroptosis-regulating ubiquitination in CVDs

Ubiquitination

MIRI

SIRT1/p53/SLC7A11

SIRT1 overexpression brought about a reduction in p53 acetylation, led to upregulation of SLC7A11, inhibits ferroptosis

[93]

MIRI

P53、TFR1

Knockdown USP7 can enhanced the ubiquitination of p53 and led to decreased levels of p53 and TFR1, reducing myocardial cell I/R injury and ferroptosis

[94]

MIRI

TRAF3

USP11 improved myocardial I/R injury by downregulating TRAF3 expression

[95]

MIRI

GPX4

Upregulation of OTUD5 deubiquitinates and stabilizes GPX4, thus reversing 4-HNE-induced ferroptosis and alleviating myocardial I/R injury

[96]

MIRI

ACSL4

YAP interacts with TEAD4 to promote the expression of NEDD4L, leading to ubiquitination of ACSL4, thereby limiting ferroptosis

[98]

MIRI

Frataxin

Reduced NHLRC1 expression can decrease frataxin ubiquitination and inhibit ferroptosis via the IRP1 pathway

[100]

DIC

Keap1

Ubiquitin E3 ligase TRIM21 negatively regulates the p62-Keap1-Nrf2 antioxidant pathway and protects doxorubicin-induced cardiotoxicity

[101]

DIC

GPX4

MITOL knockdown reduced the ratio of GSH/GSSG to regulate GPX4 expression, increase ferroptosis in cardiomyocytes

[102]

DIC

NCOA4

SPATA2 can recruit CYLD to reduce NCOA4 ubiquitination and reducing ferroptosis in doxorubicin-induced cardiotoxic cells

[103]

HF

Keap1/Nfr2

Upregulation of PGAM5 reduce Keap1 protein ubiquitination through the Keap1/Nrf2 signaling pathway, thereby reducing ferroptosis in HF

[105]