# The role of Parkin in mitophagy and dopaminergic neuron homeostasis

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,036

## Abstract

PROJECT SUMMARY/ABSTRACT
 Parkinson disease (PD) of both sporadic and genetic etiologies is associated with mitochondrial
dysfunction. In particular, the PARK genes PINK1 and Parkin, which are known to cause autosomal recessive
early-onset PD, have been implicated in the selective degradation of mitochondria by the lysosome-mediated
degradation pathway macroautophagy (MA), also known as mitophagy. Given that PINK1/Parkin-dependent
mitophagy was mechanistically characterized in invertebrate and mammalian cell-based systems, the precise
role of these genes in regulating mitochondrial quality control in the mammalian brain has remained elusive, with
constitutive loss of PINK1 or Parkin failing to robustly recapitulate key features of PD or show defective
mitochondrial handling in the rodent brain. Establishing a link between human genetics data and the mechanistic
studies in lower-order models is essential to understand the pathogenic nature of these genes and their
contribution to mitochondrial quality control and PD.
 Using a combination of mouse genetics, optical fluorescent monitoring of mitophagy, protein
biochemistry, neuropathology, and behavior, this proposal aims to build upon exciting preliminary data indicating
that the inducible loss of Parkin expression in the adult mouse leads to levodopa-responsive defects in motor
coordination and movement, and determine if the global loss of Parkin leads to a dopaminergic (DAergic) neuron-
selective neurodegeneration reminiscent of PD. Aim 1 will determine if inducible loss of Parkin in the adult animal
leads to a DAergic neuron-specific neurodegeneration and resulting PD-like neuropathology and behavior,
whereas Aim 2 will use a newly created mitophagy reporter mouse to determine if mitochondrial turnover leads
to the observed deficits. Aim 3 will build on initial observations suggesting that compensation in basal MA upon
constitutive Parkin loss masks the necessity for Parkin for mitochondrial turnover and the maintenance of central
nervous system health. Together, these studies will elucidate mechanisms of mitochondrial quality control in the
mammalian brain and provide key insight into the roles of Parkin and mitophagy in the pathogenesis of PD.

## Key facts

- **NIH application ID:** 10314222
- **Project number:** 1F31NS118897-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Christopher Joseph Griffey
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314222

## Citation

> US National Institutes of Health, RePORTER application 10314222, The role of Parkin in mitophagy and dopaminergic neuron homeostasis (1F31NS118897-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10314222. Licensed CC0.

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