Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct:159:40-46.
doi: 10.1016/j.neures.2020.01.016. Epub 2020 Feb 6.

PINK1-Parkin signaling in Parkinson's disease: Lessons from Drosophila

Yuzuru Imai  1
Affiliations
Review

PINK1-Parkin signaling in Parkinson's disease: Lessons from Drosophila

Yuzuru Imai. Neurosci Res. 2020 Oct.

Abstract

The mitochondrial protein kinase PINK1 activates Parkin ubiquitin ligase by phosphorylating Parkin and ubiquitin, which are required for mitochondrial maintenance in dopaminergic (DA) neurons whose degeneration leads to the development of Parkinson's disease (PD). Loss of PINK1 and Parkin leads to mitochondrial degeneration and abnormal wing posture in Drosophila. Modifier screening using the Drosophila wing phenotype showed that the inactivation of Miro, a mitochondrial adaptor protein, suppresses the phenotype caused by mitochondrial degeneration. When activated by PINK1, Parkin suppresses mitochondrial transport by reducing Miro levels in Drosophila DA neurons. In human DA neurons, PINK1-Parkin signaling also regulates axonal mitochondrial re-distribution in response to reduced mitochondrial membrane potential, which is impaired in the DA neurons of patients with PINK1 and Parkin mutations. Phospho-ubiquitin signals amplified by PINK1 and Parkin are stronger in DA neurons than other neurons, suggesting that PINK1-Parkin signaling is particularly important for DA neuron activity. Moreover, the recently identified PD-associated protein CHCHD2 may ensure proper electron transfer during mitochondrial respiration. The genetic interaction between PINK1/Parkin and CHCHD2 in Drosophila indicates that they are not directly associated and CHCHD2-linked PD exhibits a very different pathology to PINK1/Parkin PD. I suggest a complex pathogenesis for mitochondrial dysregulation in PD.

Keywords: Axonal transport; CHCHD2; Dopaminergic neurons; Drosophila; Mitochondria; Mitophagy; Parkinson’s disease; α-Synuclein.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The author declares no financial or other conflicts of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

LinkOut - more resources