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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,...
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...
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...
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...

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Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models
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Mutant huntingtin and mitochondrial dysfunction.

Ella Bossy-Wetzel1, Alejandra Petrilli, Andrew B Knott

  • 1University of Central Florida, Burnett School of Biomedical Sciences, College of Medicine, 4000 Central Florida Boulevard, Orlando, FL 32816, USA. ebossywe@mail.ucf.edu

Trends in Neurosciences
|October 28, 2008
PubMed
Summary

Huntington's disease (HD) involves a faulty huntingtin gene, leading to neurodegeneration. This study explores how mutant huntingtin impairs mitochondria, causing neuronal dysfunction and cell death in HD.

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Last Updated: Jun 28, 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

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene.
  • Mitochondrial dysfunction is strongly implicated in HD pathogenesis.

Purpose of the Study:

  • To elucidate the mechanisms by which mutant huntingtin (mtHtt) causes mitochondrial dysfunction in HD.
  • To explore the role of mitochondrial impairment in the selective vulnerability of neurons in HD.

Main Methods:

  • Review of existing research on mtHtt interactions with mitochondria.
  • Analysis of proposed pathways linking mtHtt to mitochondrial dysfunction, including transcriptional effects and direct interactions.
  • Examination of the impact on mitochondrial respiration, membrane potential, Ca(2+) buffering, and dynamics.

Main Results:

  • Mutant huntingtin may disrupt mitochondrial function by affecting nuclear-encoded mitochondrial proteins or directly interacting with mitochondria.
  • mtHtt can impair mitochondrial respiration, membrane potential, and calcium buffering.
  • Defects in mitochondrial dynamics, trafficking, fission, and fusion are proposed mechanisms for mtHtt neurotoxicity.

Conclusions:

  • Mitochondrial dysfunction is a central mechanism in Huntington's disease pathogenesis, driven by mutant huntingtin.
  • mtHtt-induced bioenergetic failure and impaired mitochondrial dynamics contribute to neuronal dysfunction and cell death.
  • Mitochondrial pathways may explain the selective vulnerability of specific neuronal populations, like medium spiny neurons, in HD.