Table 1. PINK1/Parkin mitophagy activators and their suggested mechanism of action.

Compound	Reported mode of action	Model system	Reference
Rho-associated Protein Kinase 2 (ROCK2) inhibitors	Elevated recruitment of hexokinase 2, a positive regulator for Parkin recruitment in depolarised mitochondria	Dopaminergic SH-SY5Y neuroblastoma cells, Drosophila model	[85]
GSK3357679A	LRRK2 inhibition	G2019S mouse model	[18]
T0466 T0467	PINK1/Parkin activity dependent, induces Parkin translocation to mitochondria	Dopaminergic neurons, muscle specific PINK1 KO in Drosophila	[96]
KTP (kinetin triphosphate) and analogues	ATP analogue with greater kinetic efficiency, enhances PINK1 activity, improves mitochondrial morphology	PINK1 knockdown Drosophila, sporadic PD rodent model	[73,93,94,96,97]
Niclosamide and analogues	reversible mitochondrial depolarisation to enhance PINK1 stabilisation and activity	Primary cortical neurons, motor neurons, HeLa cell line	[95,98]
BC1464	Disrupts FBXO7-PINK1 interaction, stabilises full length PINK1, enhances PINK1 activity	MPP+ toxicity in SH-SY5Y neuroblastoma cells, mouse primary cortical neurons, PD patient-derived fibroblasts	[100]
Gemcitabine	PINK1/MUL1 dependent mitophagy, Parkin independent	HeLa cell line	[99]
FT3967385	Selective covalent inhibition of USP30	SH-SY5Y neuroblastoma cells	[101]
MF-094	Selective inhibition of USP30 (potentially non-covalent)	isolated mitochondria from C2C12 mouse myoblasts	[102]
15-oxospiramilactone	Inhibition of USP30 activity through interaction with catalytic cystein in the active site	HeLa cell line and mouse embryonic fibroblast cells	[103]
USP30Inh-1, -2 and -3	Inactivation of USP30 via covalent linkage with catalytic cystein within the active site	SH-SY5Y neuroblastoma cells, iPSC-derived dopaminergic neurons and astrocytes, EOPD patient fibroblasts	[104]
Q14 peptide	Allosteric autoinhibition of USP30; interaction with LC3 through its LC-interacting region (LIR) to enhance autophagosome formation	A172 human glioblastoma cell line	[105]