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The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) and NIPSNAP2 accumulate on the mitochondria surface upon mitochondrial depolarization. There, they recruit proteins involved in selective autophagy, including autophagy receptors and ATG8 proteins, thereby functioning as an "eat me" signal for mitophagy. NIPSNAP1 and NIPSNAP2 have a redundant function in mitophagy and are predominantly expressed in different tissues. Zebrafish lacking a functional Nipsnap1 display reduced mitophagy in the brain and parkinsonian phenotypes, including loss of tyrosine hydroxylase (Th1)-positive dopaminergic (DA) neurons, reduced motor activity, and increased oxidative stress. • The mitochondria proteins NIPSNAP1 and NIPSNAP2 bind to autophagy-related proteins • NIPSNAP1 and NIPSNAP2 recruit autophagy receptors to depolarized mitochondria • NIPSNAP1 and NIPSNAP2, acting redundantly, are required for PARKIN-dependent mitophagy • Nipsnap1-deficient zebrafish larvae display parkinsonism Abudu and coworkers show that the mitochondrial proteins NIPSNAP1 and NIPSNAP2 are needed for PARKIN-dependent mitophagy, by facilitating recruitment of the autophagy machinery required for clearance of damaged mitochondria. Nipsnap1-deficient zebrafish larvae have a parkinsonian phenotype including accumulation of reactive oxygen species, reduced dopaminergic neurons, and a locomotion defect. [ABSTRACT FROM AUTHOR]