Related Experiment Video

Updated: Dec 30, 2025

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

18.2K

miR-218 Inhibits Mitochondrial Clearance by Targeting PRKN E3 Ubiquitin Ligase

Anthea Di Rita1,2, Teresa Maiorino1, Krenare Bruqi1,2

  • 1IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.

International Journal of Molecular Sciences
|January 18, 2020
PubMed

Insights

MicroRNA-218 (miR-218) negatively regulates mitophagy by targeting PRKN (Parkin RBR E3 ubiquitin ligase). This finding identifies miR-218 as a potential therapeutic target for diseases linked to mitophagy dysfunction.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Mitophagy, the selective removal of damaged mitochondria, is vital for cellular health.
  • The PTEN induced kinase 1 (PINK1)/Parkin RBR E3 ubiquitin ligase (PRKN) pathway is a key regulator of mitophagy.
  • Dysfunctional mitophagy is implicated in various human diseases.

Purpose of the Study:

  • To investigate the role of microRNA-218 (miR-218) in the PINK1/PRKN-mediated mitophagy pathway.
  • To determine if miR-218 acts as a negative regulator of mitophagy.
  • To explore the therapeutic potential of targeting miR-218 in diseases associated with mitophagy defects.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess PRKN mRNA levels.
  • Western blotting to evaluate PRKN protein levels.
  • Mitochondrial ubiquitylation assays and autophagy flux measurements to assess mitophagy efficiency.

Main Results:

  • Overexpression of miR-218 significantly reduced PRKN mRNA and protein levels.
  • miR-218 overexpression led to decreased mitochondrial ubiquitylation.
  • Impaired mitochondrial clearance and mitophagy defects were observed upon miR-218 overexpression.

Conclusions:

  • miR-218 negatively regulates the PINK1/PRKN-mediated mitophagy pathway by targeting PRKN.
  • Defects in mitophagy caused by miR-218 overexpression highlight its critical role in mitochondrial quality control.
  • miR-218 represents a potential therapeutic target for diseases characterized by mitophagy dysfunction.
Keywords:
PARKIN/PRKNmiR-218microRNAmitochondriamitophagy

More Related Videos

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge09:53

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge

Published on: June 15, 2018

7.9K
Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay08:40

Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay

Published on: May 2, 2019

6.2K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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,...
11.7K
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
19.4K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.6K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.8K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
18.3K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.5K