Table 1.

Proteins implicated in the OMMAD pathway

Protein	Biological function	Role in OMMAD/Targets	References
Parkin	IBR-domain E3 Ub ligase	ubiquitination of Mfn1, Mfn2 and VDAC1; induces mitochondria-specific auophagy	[13,41–43]
PINK1	mitochondrial kinase	recruits Parkin to the mitochondria	[61,62]
MARCH5/MARCH-V/Mitol	mitochondrial RING-domain E3 Ub ligase	Binds and ubiquitinate Drp1 (mitochondrial fission factor) and Mitofusins (mitochondrial fusion factors); mitochondrial dynamics regulation	[45–47]
MULAN/MAPL	mitochondrial RING-domain E3 Ub ligase	mitochondrial dynamics regulation; reported also as E3 SUMO ligase targeting Drp1	[63,64]
IBRDC2	IBR-domain E3 Ub ligase	apoptosis regulation; targets Bax, a proapoptotic protein in Bcl2 family	[21]
Mule/ARF-BP1	HECT domain E3 Ub ligase	ubiquitinates and regulates turnover of Mcl1, an antiapoptotic protein in Bcl2 family	[18]
USP9x	deubiquitinase	deubiquitinates and regulates turnover of Mcl1	[19]
USP30	mitochondrial deubiquitinase	regulates mitochondrial dynamics; substrates unknown	[60]
p97/CDC48	AAA-ATPase; protein dislocase	regulates OMM protein turnover and mitochondria-specific autophagy in yeast and mammals	[13,37,54]
Vms1p	adaptor protein	cofactor of CDC48; regulates OMM protein and mitochondrial degradation in yeast	[54]
Npl4	adaptor protein	cofactor of CDC48; regulates OMM protein and mitochondrial degradation in yeast	[54]
Proteasome	protein degradation complex	translocates to the mitochondria upon activation of Parkin-dependent, mitochondrial stress-induced mitophagy	[38]