Related Experiment Video

Updated: Jun 21, 2026

Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model
06:07

Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model

Published on: June 23, 2023

Role of mitochondrial dysfunction in the pathogenesis of Huntington's disease

Rodrigo A Quintanilla1, Gail V W Johnson

  • 1Department of Anesthesiology, University of Rochester, Rochester, NY 14642-0002, USA.

Brain Research Bulletin
|July 23, 2009
PubMed

Insights

Huntington's disease (HD) involves CAG repeat expansion in huntingtin protein, impairing mitochondrial function. This leads to energy deficits, oxidative stress, and neuronal death, highlighting mitochondria's role in HD pathogenesis.

Area of Science:

  • Neurodegenerative Disorders
  • Mitochondrial Biology
  • Molecular Genetics

Background:

  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder.
  • It is caused by a CAG repeat expansion in the huntingtin gene.
  • The precise pathogenic mechanisms remain under investigation, but mitochondrial dysfunction is implicated.

Purpose of the Study:

  • To review evidence linking mutant huntingtin to mitochondrial dysfunction in HD.
  • To explore how impaired mitochondrial function contributes to neuronal death in HD.
  • To examine the role of calcium homeostasis alterations in HD pathogenesis.

Main Methods:

  • Review of existing literature on HD, huntingtin protein, and mitochondrial function.
  • Analysis of studies investigating mitochondrial calcium uptake and respiration in HD models.
  • Examination of research on oxidative stress and energy metabolism in HD.

Main Results:

  • Mutant huntingtin directly or indirectly impairs mitochondrial function.
  • Mitochondria in HD models exhibit altered calcium uptake and respiration.
  • Compromised energy metabolism and increased oxidative damage are observed in HD.

Conclusions:

  • Mitochondrial dysfunction is a key contributor to neuronal dysfunction and death in HD.
  • Impaired mitochondrial calcium handling affects cellular homeostasis in HD.
  • Targeting mitochondrial pathways may offer therapeutic strategies for HD.

More Related Videos

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models08:48

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models

Published on: June 30, 2023

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
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...
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...
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,...