Related Experiment Video
Updated: Apr 18, 2026

Author Spotlight: Fluorescence-Based Quantification of Mitochondrial Membrane Potential and Superoxide Levels Using Live Imaging in HeLa Cells
Published on: May 12, 2023
PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane
Stephan Gehrke1, Zhihao Wu1, Michael Klinkenberg2
1Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
Mitochondria play essential roles in many aspects of biology, and their dysfunction has been linked to diverse diseases. Central to mitochondrial function is oxidative phosphorylation (OXPHOS), accomplished by respiratory chain complexes (RCCs) encoded by nuclear and mitochondrial genomes. How RCC biogenesis is regulated in metazoans is poorly understood. Here we show that Parkinson's disease (PD)-associated genes PINK1 and Parkin direct localized translation of certain nuclear-encoded RCC (nRCC) mRNAs. Translationally repressed nRCC mRNAs are localized in a PINK1/Tom20-dependent manner to mitochondrial outer membrane, where they are derepressed and activated by PINK1/Parkin through displacement of translation repressors, including Pumilio and Glorund/hnRNP-F, a Parkin substrate, and enhanced binding of activators such as eIF4G. Inhibiting the translation repressors rescued nRCC mRNA translation and neuromuscular-degeneration phenotypes of PINK1 mutant, whereas inhibiting eIF4G had opposite effects. Our results reveal previously unknown functions of PINK1/Parkin in RNA metabolism and suggest new approaches to mitochondrial restoration and disease intervention.
Insights
Parkinson
Area of Science:
- Mitochondrial Biology
- Neuroscience
- Molecular Genetics
Background:
- Mitochondrial dysfunction is implicated in various diseases.
- Oxidative phosphorylation (OXPHOS) relies on respiratory chain complexes (RCCs).
- Regulation of RCC biogenesis in metazoans remains unclear.
Purpose of the Study:
- Investigate the roles of Parkinson's disease (PD)-associated genes PINK1 and Parkin.
- Elucidate the regulation of nuclear-encoded RCC (nRCC) mRNA translation and localization.
- Explore potential therapeutic strategies for mitochondrial dysfunction.
Main Methods:
- Utilized techniques to study mRNA localization and translation.
- Investigated the interaction of PINK1 and Parkin with translation machinery.
- Employed genetic manipulation to assess the impact on nRCC mRNA and cellular phenotypes.
Main Results:
- PINK1 and Parkin regulate the localized translation of nRCC mRNAs.
- nRCC mRNAs are targeted to the mitochondrial outer membrane in a PINK1/Tom20-dependent manner.
- PINK1/Parkin displace repressors (e.g., Pumilio, hnRNP-F) and recruit activators (e.g., eIF4G) for mRNA derepression.
Conclusions:
- PINK1 and Parkin have novel functions in RNA metabolism.
- Mitochondrial localization and translation control are critical for nRCC biogenesis.
- Findings suggest new therapeutic avenues for mitochondrial diseases and PD.
More Related Videos
15:09The Use of Primary Human Fibroblasts for Monitoring Mitochondrial Phenotypes in the Field of Parkinson's Disease
Published on: October 3, 2012
09:53Author Spotlight: Advancing Techniques and Discoveries in Protein Synthesis and Assembly Through Innovative Mitochondrial Research
Published on: June 7, 2024
Related Concept Videos
Porin Insertion in the Outer Mitochondrial Membrane
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Structure of Porins
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Mitochondrial Precursor Proteins
Most of the mitochondrial...
The Inner Mitochondrial Membrane