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Related Concept Videos

Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
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 precursors...

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Related Experiment Video

Updated: Jun 27, 2026

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
08:56

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Published on: October 10, 2025

Variable mitochondrial phenotypes and reduced complex IV assembly factor SCO2 in LRRK2-G2019S fibroblasts.

Ruby Wallis1, Ella Simmonite1, Harry Cooper1

  • 1Sheffield Institute for Translational Neuroscience (SITraN), School of Medicine and Population Health, Faculty of Health, University of Sheffield, 385a Glossop Road, S10 2HQ, Sheffield, UK.

Scientific Reports
|June 25, 2026
PubMed
Summary

The LRRK2-G2019S mutation, common in Parkinson's disease, may cause mitochondrial complex IV deficiency. This deficiency, linked to reduced SCO2 expression, appears specific to manifesting carriers, suggesting a pathogenic mechanism.

Keywords:
G2019S mutationLeucine-rich repeat kinase-2 (LRRK2)ManifestingMitochondriaNon-manifestingParkinson’s diseasePenetrance

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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • The Leucine-Rich Repeat Kinase 2 (LRRK2) gene harbors the G2019S mutation, a frequent cause of familial Parkinson's disease (PD).
  • LRRK2-G2019S exhibits incomplete penetrance, meaning not all carriers develop PD, and its underlying molecular mechanisms remain unclear.
  • Mitochondrial dysfunction is implicated in PD pathogenesis, but the specific role of LRRK2 mutations in this process requires further investigation.

Purpose of the Study:

  • To investigate the mitochondrial effects associated with LRRK2-G2019S penetrance.
  • To compare patient-derived fibroblasts from manifesting and non-manifesting LRRK2-G2019S carriers with controls to elucidate the mutation's pathogenic mechanism.
  • To identify specific molecular alterations in mitochondria linked to LRRK2-G2019S-associated PD.

Main Methods:

  • Utilized patient-derived fibroblasts from manifesting and non-manifesting LRRK2-G2019S carriers and controls.
  • Quantified the expression of the complex IV assembly factor SCO2 and complex IV subunits.
  • Assessed unbound mitochondrial copper content, mitochondrial morphology, membrane potential, ATP production, and reactive oxygen species (ROS) generation.

Main Results:

  • A significant 50% reduction in SCO2 expression was observed in manifesting LRRK2-G2019S fibroblasts, but not in non-manifesting carriers.
  • Manifesting carriers showed a minor decrease in complex IV subunit expression alongside reduced SCO2.
  • No significant differences in mitochondrial copper, morphology, membrane potential, ATP, or ROS levels were found between manifesting and non-manifesting carriers, indicating cellular phenotype heterogeneity.

Conclusions:

  • Mitochondrial complex IV deficiency, potentially due to reduced SCO2, may be a pathogenic mechanism in LRRK2-G2019S-associated Parkinson's disease.
  • The observed heterogeneity in cellular phenotypes suggests the presence of compensatory mechanisms in LRRK2-G2019S carriers.
  • Further research is needed to fully understand the interplay between SCO2, complex IV function, and PD development in LRRK2 mutation carriers.