Aberrant　mitophagy　has　been　implicated　in　a　broad　spectrum　of　disorders.　PINK1,　Parkin,　and　ubiquitin　have　pivotal　roles　in　priming　mitophagy.　However,　the　entire　regulatory　landscape　and　the　precise　control　mechanisms　of　mitophagy　remain　to　be　elucidated.　Here,　we　uncover　fundamental　mitophagy　regulation　involving　PINK1　and　a　non-canonical　role　of　the　mitochondrial　Tu　translation　elongation　factor　(TUFm).　The　mitochondrion-cytosol　dual-localized　TUFm　interacts　with　PINK1　biochemically　and　genetically,　which　is　an　evolutionarily　conserved　Parkin-independent　route　toward　mitophagy.　A　PINK1-dependent　TUFm　phosphoswitch　at　Ser222　determines　conversion　from　activating　to　suppressing　mitophagy.　PINK1　modulates　differential　translocation　of　TUFm　because　p-S222-TUFm　is　restricted　predominantly　to　the　cytosol,　where　it　inhibits-mitophagy　by　impeding　Atg5-Atg12　formation.　The　self-antagonizing　feature　of　PINK1/TUFm　is　critical　for　the　robustness　of　mitophagy　regulation,　achieved　by　the　unique　kinetic　parameters　of　p-S222-TUFm,　p-S65-ubiquitin,　and　their　common　kinase　PINK1.　Our　findings　provide　new　mechanistic　insights　into　mitophagy　and　mitophagy-associated　disorders.