Related Experiment Video

Updated: Dec 20, 2025

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights
07:55

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights

Published on: June 16, 2023

1.8K

Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic

Cristiane Benincá1,2, Vanessa Zanette2, Michele Brischigliaro3

  • 1Medical Research Council, Mitochondrial Biology Unit, Cambridge, Cambridgeshire, UK.

Journal of Medical Genetics
|May 23, 2020
PubMed
Abstract

Insights

A mutation in the APOO gene disrupts MIC26 protein, impairing mitochondrial structure and function, leading to severe neuromuscular and developmental disorders in a human family and model organisms.

Area of Science:

  • Mitochondrial biology
  • Genetics
  • Neuroscience

Background:

  • Mitochondria generate ATP via oxidative phosphorylation in the inner mitochondrial membrane (IMM).
  • The mitochondrial contact site and organising system (MICOS) complex maintains IMM architecture.
  • APOO encodes MIC26, a MICOS component with an incompletely understood role in assembly and maintenance.

Purpose of the Study:

  • Investigate the function of MIC26 in mitochondrial maintenance.
  • Identify genetic variants in APOO associated with severe developmental disorders.
  • Elucidate the molecular mechanisms linking APOO mutations to mitochondrial dysfunction.

Main Methods:

  • Whole exome sequencing in a family with affected members.
  • Analysis of patient-derived skin fibroblasts.
  • Creation and analysis of knockout models in yeast and Drosophila melanogaster.

Main Results:

  • A pathogenic c.350T>C variant in APOO, causing an I117T substitution in MIC26, was identified.
  • The mutation led to impaired MIC26 processing, faulty IMM insertion, altered MICOS assembly, and cristae junction disruption.
  • MIC26 dysfunction caused mitochondrial structural and functional deficits in yeast and Drosophila models.

Conclusions:

  • This study reports the first pathogenic mutation in APOO, linking it to altered MICOS assembly and neuromuscular impairment.
  • MIC26 is crucial for MICOS assembly and stability in humans, yeast, and flies.
  • APOO mutations represent a novel cause of mitochondrial disease.
Keywords:
clinical geneticsgeneticsmetabolic disordersneuromuscular disease

More Related Videos

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry06:53

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry

Published on: November 23, 2011

37.5K
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.1K

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...
8.8K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
4.3K
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...
16.4K