Table 1.

Effects of common anti-rheumatic drugs on mitochondrial homeostasis.

Drugs	Action point	Effect on mitochondria	Impact on RA	References
Mitochondrial biogenesis
MTX	Folate-dependent ↓	Inhibits mitochondrial folate synthesis	Inhibits synovial cell proliferation	(144)
Quercetin	PGC-1α ↓	Promotes mtDNA	Inhibits TNF-α, IL-6, etc.	(39)
Resveratrol	PGC-1α ↓	Promotes mtDNA	Corrects RA metabolic disorders	(40)
2-DG	Glycolysis ↓	Activates AMPK and improves energy metabolism	Inhibits NF-κB	(148)
Tofacitinib	JAK ↓	Reverses mitochondrial membrane potential	Lowers glycolytic enzyme genes	(152)
IRF9	SIRT1 ↑	Reverses mitochondrial membrane potential and increases in membrane permeability	NF-κB inhibition and pro-apoptosis	(151)
Cantleyoside	SIRT1 ↑	Suppresses OCR and ECAR	NF-κB inhibition and pro-apoptosis	(151)
Metformin	ETC complexes ↑	Reduces mitochondrial activity and ATP production	Inhibits synovial cell proliferation	(153)
Mitochondrial dynamics
mdivi-1	DNM1L ↓	Promotes mitochondrial division	Promotes apoptosis of synovial cells	(83)
Leflunomide	DHODH ↓	Inhibits DHODH, promotes Mfn1, Mfn2, and increases mitochondrial fusion	Reduces oxidative stress and inhibits proliferation	(143)
Sulfasalazine		Increases mitochondrial membrane permeability	Induces T-cell apoptosis	(144)
TNF-a inhibitor	TNF-a ↓	Reduces mitochondrial division	Reduces oxidative stress	(109)
Icariside		Reverses mitochondrial membrane potential	Induces RA-FLS apoptosis	(120)
7-HT		Enhances mitochondrial pathway Bax/Bcl-2	Induces apoptosis in FLS cells	(121)
β-Elmene		Phosphorylates MAPK pathway	Induces apoptosis	(123)
Mitochondrial autophagy
5-azacytidine	Methylation ↓	Enhances PINK1-mediated mitochondrial autophagy	Inhibits cytokines and chemokines	(65)
Rapamycin	mTOR ↑	Enhances mitochondrial autophagic activity in synovial cells	Inhibits cytokines	(154)