Related Experiment Video

Updated: May 2, 2026

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
06:05

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Published on: March 9, 2022

3.8K

Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious

Jahda H Hill1, Zhe Chen1, Hong Xu2

  • 11] Laboratory of Molecular Genetics, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA. [2].

Nature Genetics
|March 12, 2014
PubMed

Insights

Healthy mitochondria are preferentially amplified during egg development in fruit flies. This process, occurring early in oogenesis, prevents the inheritance of harmful mitochondrial DNA mutations.

Area of Science:

  • Genetics
  • Developmental Biology
  • Mitochondrial Biology

Background:

  • Mitochondrial DNA (mtDNA) mutations are common, yet severe mutations are rare, suggesting protective mechanisms.
  • Strong purifying selection exists in the mouse female germline, but positive selection mechanisms for healthy mitochondria are unclear.

Purpose of the Study:

  • To investigate the mechanisms of positive selection for healthy mitochondria during Drosophila melanogaster oogenesis.
  • To understand how wild-type mitochondrial DNA is amplified and deleterious mutations are eliminated.

Main Methods:

  • Visualizing mtDNA replication during oogenesis in Drosophila melanogaster.
  • Isolating and characterizing a temperature-sensitive lethal mtDNA allele (mt:CoI(T300I)).
  • Assessing the frequency of the mutant allele in heteroplasmic flies at different temperatures and developmental stages.

Main Results:

  • Mitochondrial DNA replication begins before oocyte determination in the germarium and depends on mitochondrial fitness.
  • The mt:CoI(T300I) allele reduced mtDNA replication at the restrictive temperature.
  • Selection against the mt:CoI(T300I) allele occurred during oogenesis and across generations, coinciding with selective mtDNA replication.

Conclusions:

  • A novel developmental mechanism for selective amplification of wild-type mtDNA exists in Drosophila oogenesis.
  • This mechanism, involving selection during germline mtDNA replication, may prevent the transmission of harmful mitochondrial mutations and is potentially evolutionarily conserved.

More Related Videos

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

2.0K
Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines07:49

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

3.0K

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...
7.8K
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
3.1K
Non-nuclear Inheritance01:29

Non-nuclear Inheritance

Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
20.7K
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...
2.9K
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,...
8.8K
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...
16.0K