Table 1.

Regulatory molecules of mitophagy in IVDD and OA

Regulators	Target cell/tissue	Mitophagy pathway	Main findings	Reference
IVDD↓ PRKN	Rat NP cells	PRKN-mediated mitophagy↓	Knockdown of Prkn promotes TNF-stimulated mitochondria-induced ROS generation and aggravates apoptosis of NP cells.	[17]
PINK1↓	Human NP cells	PRKN-mediated mitophagy↓	Aggravates NP cells senescence under oxidative stress	[63]
PRKN↓	Human endplate chondrocytes	PRKN-mediated mitophagy↓	Accelerates mitochondrial dysfunction and apoptosis in endplate chondrocytes under oxidative stress	[64]
MFN2↑	Rat NP cells	PRKN-mediated mitophagy↑	Overexpression of Mfn2 attenuates cell damage and the development of IVDD in rats	[66]
circErcc2↑	Rat NP cells	Mir182-5p-SIRT1-PRKN -mediated mitophagy↑	Attenuates apoptosis, ECM degradation and enhances mitophagy in response to oxidative stress and retards IVDD in rats.	[68]
FOXO3↑	Rat NP cells	PRKN-mediated mitophagy↑	Inhibits mitochondrial dysfunction, cell apoptosis and ECM degradation under nutrient deficiency	[86
NDUFA4L2↑	Rat NP cells	PRKN-mediated mitophagy↓	Facilitates the survival of NP cells by repressing excessive mitophagy, and alleviates IVDD in rats	[62]
PPARGC1A↑	Rat AF cells	SIRT2-PPARGC1A-PRKN -mediated mitophagy↓	Protect AF cells against apoptosis under oxidative stress	[87]
OA PRKN↓	Human chondrocytes	PRKN-mediated mitophagy↓	Depletion of PRKN increases mitochondrial dysfunction and oxidative stress under the IL1B stimulation	[18]
PRKN↑	Human chondrocytes	PRKN-mediated mitophagy↑	PRKN overexpression reduces mitochondrial ROS and apoptosis of chondrocyte through the clearance of dysfunctional mitochondria	[18]
PHF23↓	C28/I2 chondrocytes	PRKN-mediated mitophagy↑	PHF23 deficiency reduces in IL1B-induced ECM degradation.	[91]
A2AR↓	Murine chondrocytes	Mitophagy↓	Promotes mitochondrial swelling and dysfunction with increased ROS burden and diminished mitophagy	[96]
PINK1↓	Mice cartilage	PINK1-mediated mitophagy↓	Reduces cartilage damage and pain behaviors in pink1-knockout mice with MIA-induced OA	[88]