Translational neurodegenerationSep 18, 2026

Different Activities of the PINK1-Parkin System in Various Species

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 19, 2026

Abstract

Effective knockdown of PINK1 or parkin in non-human primates induces dopaminergic neuron loss in the substantia nigra.

Loss-of-function mutations in PINK1 or parkin are linked to early-onset Parkinson's disease.
Animal models with PINK1 or parkin knockout have not consistently reproduced neurodegeneration seen in human patients.
Substantial protein depletion of PINK1 or parkin is necessary to observe effects on neuron loss and pathology.
The activity of the PINK1-parkin pathway may vary between species, influencing disease outcomes.
The review highlights the diverse roles of the PINK1-parkin axis beyond its known function in mitophagy.

Simplified

In vitro studies have established that PTEN-induced putative kinase 1 (PINK1) and parkin are central regulators of mitophagy, and loss-of-function mutations in either gene can cause early-onset Parkinson's disease (PD). Although various animal models, including mice and pigs with PINK1 or PRKN knockout, have largely failed to recapitulate the neurodegeneration seen in PD patients, effective knockdown of PINK1 or PRKN in non-human primates, when achieving substantial protein depletion, does induce dopaminergic neuron loss in the substantia nigra and α‑synuclein pathology, suggesting that both the degree of protein loss and the species-dependent PINK1-parkin axis activity contribute to PD pathogenesis. This review compares pathological and behavioral outcomes of PINK1- and parkin-deficient animal models across species, illustrates diverse functions of the PINK1-parkin axis beyond mitophagy, discusses mechanisms underlying the species-dependent differences, and highlights the therapeutic potential of targeting this pathway. The review also underscores the necessity of considering species-specific mechanisms when investigating the PINK1/parkin pathway.

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Different Activities of the PINK1-Parkin System in Various Species

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