Related Experiment Video

Updated: Jun 20, 2026

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

GDAP1 mutations differ in their effects on mitochondrial dynamics and apoptosis depending on the mode of inheritance

Axel Niemann1, Konstanze Marion Wagner, Marcel Ruegg

  • 1Institute of Cell Biology, Department of Biology, ETH Zürich, Switzerland. axel.niemann@cell.biol.ethz.ch

Neurobiology of Disease
|September 29, 2009
PubMed

Insights

Mutations in the GDAP1 gene cause Charcot-Marie-Tooth disease (CMT) by affecting mitochondrial dynamics. Recessive mutations reduce mitochondrial fission, while dominant mutations impair fusion, leading to cell damage and disease.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Genetics

Background:

  • Mutations in the GDAP1 gene are linked to inherited peripheral neuropathies, specifically Charcot-Marie-Tooth disease (CMT).
  • Mitochondrial dynamics, including fission and fusion, are crucial for cellular health and function.
  • The precise role of GDAP1 in mitochondrial dynamics and its contribution to CMT pathogenesis remain incompletely understood.

Purpose of the Study:

  • To elucidate the function of the GDAP1 gene in mitochondrial fission and fusion processes.
  • To investigate how different GDAP1 mutations (recessive vs. dominant) impact mitochondrial dynamics and cellular viability.
  • To understand the distinct cellular mechanisms underlying CMT caused by GDAP1 mutations.

Main Methods:

  • Overexpression and knockdown of GDAP1 in cellular models.
  • Assessment of mitochondrial fission and fusion activities.
  • Analysis of cellular susceptibility to apoptosis and reactive oxygen species (ROS) production.
  • Evaluation of mitochondrial transmembrane potentials.

Main Results:

  • GDAP1 functions as a mitochondrial fission factor, dependent on Drp1 and Fis1.
  • GDAP1 mutations associated with recessive CMT (rmGDAP1s) exhibit reduced fission activity.
  • GDAP1 mutations associated with dominant CMT (dmGDAP1s) interfere with mitochondrial fusion, increase ROS, disrupt mitochondrial potential, and enhance apoptosis susceptibility.
  • Wild-type GDAP1 promotes fission without increasing apoptosis risk.

Conclusions:

  • GDAP1 is a key regulator of mitochondrial fission.
  • Recessive GDAP1 mutations impair mitochondrial fission, while dominant mutations disrupt mitochondrial fusion and induce mitochondrial damage.
  • Distinct alterations in mitochondrial dynamics underlie the pathogenesis of CMT, depending on the mode of GDAP1 mutation inheritance.

More Related Videos

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs08:15

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs

Published on: August 15, 2025

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...
Mutations01:39

Mutations

Overview
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
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...
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.