TABLE 2.

The regulatory roles, molecular mechanisms, and research background of sirtuins in ferroptosis.

Gene	Signal pathway	Effect on ferroptosis	Mechanism	Background	Ref
SIRT1	USP22-SIRT1-p53/SLC7A11	inhibit	USP22 inhibited ferroptosis via SIRT1-p53/SLC7A11 pathway	cardiomyocyte	Ma et al. (2020)
	SIRT1-p53/ACSL4-GPX4/SLC7A11	inhibit	Overexpression of SIRT1 inhibited lipid peroxidation and diminished MDA levels, reversed SLC7A11 and GPX4 downregulation, ACSL4 and acetylated p53 upregulation to inhibit ferroptosis	lung epithelial cells	Chen et al. (2022b)
	MiR-138-5p-SIRT1/NRF2	inhibit	MiR-138-5p inhibited the activity of SIRT1 and NRF2 to promote ferroptosis	diabetic retinopathy	Tang et al. (2022)
	SIRT1-NRF2-HO-1/GPX-4	inhibit	Edaravone ameliorated ferroptosis via SIRT1/NRF2/HO-1/GPX-4 pathway	depressive and anxiety-like behaviors	Dang et al. (2022)
	SIRT1/NRF2	inhibit	Fisetin attenuated cardiomyopathy by inhibiting ferroptosis through SIRT1/NRF2 signaling pathway activation	cardiomyopathy	Li et al. (2021)
	SIRT1/NRF2/HO-1	inhibit	Ulinastatin protected against liver injury by alleviating ferroptosis via the SIRT1/NRF2/HO-1 pathway	liver injury	Wang et al. (2021b)
	SIRT1/NRF2/HO-1	Inhibit	Activation of SIRT1/NRF2/HO-1 signaling pathway inhibited ferroptosis	hippocampus	Liu et al. (2022a)
	SIRT1	promote	Intestinal SIRT1 deficiency protected mice by mitigating ferroptosis	liver injury	Zhou et al. (2020b)
	SIRT1	promote	Inhibiting the expression and activity of SIRT1 can inhibit ferroptosis	head and neck cancer	Lee et al. (2020)
	SIRT1	promote	BRD4 inhibitor (+)-JQ1 induced ferroptosis by enhancing the expression of SIRT1	cancer	Sui et al. (2019)
	MiR-34a-5p/SIRT1	inhibit	MiR-34a-5p inhibited the expression of SIRT1 to induce ferroptosis	PC12 cells	Hao et al. (2022)
	SIRT1/GPX4	inhibit	Calorie restriction protected against contrast-induced nephropathy via SIRT1/GPX4 activation	nephropathy	Fang et al. (2021)
	SIRT1-autophagy axis	inhibit	SIRT1 inhibited the ferroptosis of foam cells in excess iron by autophagy	atherosclerosis	Su et al. (2021)
	SIRT1-autophagy axis	inhibit	SIRT1-autophagy axis inhibited oxidative stress-induced ferroptosis	human nucleus pulposus cells	Zhou and Ruan (2022)
	SIRT1/NRF2	inhibit	Activating SIRT1 and upregulating the expression of NRF2 can against ferroptosis	sepsis-induced cardiomyopathy	Zeng et al. (2023)
	SIRT1	inhibit	Mitochondrial damage resulted from SIRT1 inactivation plays an important role in ferroptosis	schwan cells	Liang et al. (2023)
	SIRT1/SLC7A11	inhibit	PUM2 promoted ferroptosis by inhibiting SIRT1/SLC7A11	neuroinflamma-tion and brain damage	Liu et al. (2023)
	SIRT1	promote	Sodium fluoride upregulated SIRT1 and promoted ferroptosis	liver in chicken	Wang et al. (2023)
SIRT2	SIRT2-FPN1/GPX4/ACSL4	inhibit	Overexpression of SIRT2 inhibited ferroptosis by regulating FPN1, GPX4, ACSL4, iron accumulation and oxidant stress	neuropathic pain	Zhang et al. (2022c)
	SIRT2-P53	inhibit	SIRT2 inhibition exacerbated p53-mediated ferroptosis	traumatic brain injury	Gao et al. (2021)
SIRT3	SIRT3-P53	inhibit	SIRT3 deacetylation p53 to inhibit ferroptosis induced by ROS.	osteosarcoma	Jin et al. (2021)
	SIRT3	Inhibit	Knocking down SIRT3 inhibited ferroptosis to reduce oligodendrocytes survival	oligodendrocytes	Novgorodov et al. (2018)
	MKD-SIRT3	inhibit	MKD inhibited ferroptosis maybe by promoting the expression of SIRT3	cognitive deficiency	Wang et al. (2022)
	SIRT3- AMPK-mTOR/SIRT3-GPX4	promote	SIRT3 deficiency inhibited the AMPK/mTOR pathway and promoted GPX4 levels to suppress ferroptosis	gestational diabetes mellitus	Han et al. (2020)
	SIRT3-AKT	promote	Silence of SIRT3 gene inhibited AKT-dependent ferroptosis	gallbladder cancer	Liu et al. (2021b)
	AKT-SIRT3/SOD2	inhibit	LCZ696 increased the expression of SIRT3 and deacetylated its target gene SOD2 by activating AKT, thereby inhibiting ferroptosis	cardiac toxicity	Liu et al. (2022b)
	NRF2/SIRT3/iNOS	inhibit	Inactivating the NRF2/SIRT3 signaling pathway through ROS, thereby promoting the expression of iNOS, ultimately leading to ferroptosis	bronchial epithelial cells	Zi et al. (2023)
	SIRT3/AMPK/mTOR	inhibit	Activating the SIRT3/AMPK/mTOR pathway can inhibit ferroptosis	polycystic ovary syndrome	Peng et al. (2023)
SIRT6	SIRT6-Keap1/NRF2/GPX4	promote	SIRT6 silencing inactived Keap1/NRF2 signalling pathway and suppressed GPX4 to drive ferroptosis	gastric cancer	Cai et al. (2021)
	SIRT6	inhibit	Sodium hydrosulfide (NaHS) upregulated the expression and activity of SIRT6 to suppress ferroptosis	type 1 diabetic	Wang et al. (2021c)
	SIRT6-NF-κB	promote	SIRT6 promoted ferroptosis in pancreatic cancer by regulating the expression NF-κB	pancreatic cancer	Gong et al. (2022)
	SIRT6-SLC7A11/GPX4/GSH	inhibit	SIRT6 overexpression could reverse the decrease of GPX4, SLC7A11, and GSH and reduce MDA and ROS to inhibit ferroptosis	glucocorticoid-Induced osteonecrosis	Fang et al. (2022)
	SIRT6/p-NRF2/GPX4 and SIRT6/NCOA4/FTH1	inhibit	SIRT6/p-NRF2/GPX4 and SIRT6/NCOA4/FTH1 can inhibit ferroptosis	rat lens epithelial cells	Mi et al. (2023)
SIRT7	SIRT7/KLF15/NRF2	inhibit	SIRT7 can alleviate renal ferroptosis by promoting the KLF15/NRF2 signaling pathway	chronic renal diseases	Li et al. (2022)