Related Experiment Video

Updated: Jun 1, 2026

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models
08:48

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

Published on: June 30, 2023

Huntington's disease, calcium, and mitochondria

Marta Giacomello1, Roman Hudec, Raffaele Lopreiato

  • 1Venetian Institute of Molecular Medicine, Padova, Italy.

Biofactors (Oxford, England)
|June 16, 2011
PubMed

Insights

Huntington's disease (HD) stems from a mutated Huntingtin (Htt) gene, causing neuronal dysfunction. This overview highlights the role of calcium and mitochondrial stress in HD pathogenesis.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion in the Huntingtin (Htt) gene.
  • This mutation leads to a polyQ expansion in the Htt protein, resulting in motor and cognitive impairments.

Purpose of the Study:

  • To provide an overview of Huntingtin protein alterations in HD.
  • To explore the impact of Htt mutations on gene transcription and neuronal calcium homeostasis.
  • To emphasize the critical role of mitochondria in HD molecular pathogenesis.

Main Methods:

  • Review of existing literature on Huntington's disease molecular pathology.
  • Analysis of cellular and animal models for HD research.
  • Focus on biochemical changes in HD neurons, particularly in the striatum.

Main Results:

  • Htt mutation leads to pathological polyQ expansion and widespread Htt protein changes.
  • Dysregulation of neuronal calcium (Ca2+) homeostasis is a key feature in HD.
  • Mitochondrial stress and dysfunction are implicated in the disease's progression.

Conclusions:

  • The molecular etiology of HD involves complex interactions between Htt protein dysfunction, altered gene transcription, and disrupted cellular homeostasis.
  • Mitochondrial dysfunction is a central factor in the pathogenesis of Huntington's disease.
  • Understanding these molecular mechanisms is crucial for developing effective HD therapies.

More Related Videos

Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers10:31

Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers

Published on: September 29, 2017

Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model06:07

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

Published on: June 23, 2023

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,...
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...
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,...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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,...
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...