Research projects finished

A study of the pathogenicity of a new gene


3 años


30,000 por año


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A study of the pathogenicity of mutations found in a new gene related to mitochondrial pathology.

Presented by: María Pilar Bayona Bafaluy
Lecturer in the Department of Biochemistry and Molecular Biology and a member of the Mitochondrial Biogenesis and Pathology research group at the University of Zaragoza, which is led by Dr Julio Montoya Villarroya.


Mitochondrial oxidative phosphorylation (OxPhos) is a metabolic process essential to life, which provides most of the useful energy to the body’s cells. The maintenance of this function is specific to each cell, since it depends on contributions from the nuclear genome, which codes the great majority of mitochondrial proteins, and from the mitochondrial genome, which codes a limited but essential group of components of the OxPhos system. Defects in its function generate respiratory chain diseases (RCD), which are very difficult to diagnose owing to the great clinical heterogeneity displayed by patients. However, a large part of what we know about the activity and regulation of the OsPhos system comes from the study of patients with particular defects.

The use of modern mass sequencing techniques has enabled us to identify genetic variations in the genome of many patients. This does not always lead to a molecular diagnosis because the interpretation of variations in DNA can prove to be highly complex. In some cases they affect proteins whose function is unknown, or they are not related to the biological route affected.

In this project we propose to study at molecular level the relation to the OxPhos system of a defective protein in a patient with a suspected mitochondrial disease. The function of the protein in question is as yet unknown. From a structural point of view, OxPhos activity takes place in the internal mitochondrial membrane, which is where this protein seems to be located. The information obtained from biomedical data bases indicates that the protein has low expression and that it originated during evolution by genetic duplication of a gene that has previously been found altered in a patient with mitochondrial disease. In the patient we have found a second mutation with less probability of being the etiological factor of the disease, which we will also analyze because of the heterogeneity of mitochondrial pathologies.

The aims of the project

The overall objective of this project is to describe the cellular function of the ATAD3C protein and its relation to OxPhos function. This will allow a molecular diagnosis of the patient affected, in addition to the possibility of developing a personalized therapy.

The specific aims are:
1. To analyze the effects of the defective ATAD3C protein on OxPhos function and on mitochondrial dynamics using fibroblasts derived from the patient.
2. To study the effect of eliminating the ATAD3C protein on OxPhos function and on mitochondrial dynamics in model cell lines in which their expression will be eliminated through genetic engineering (RNAi and/or CRISPR/Cas9).
3. To clone the protein in order to study the effect of its over-expression on OxPhos function and mitochondrial dynamics, both in the patient’s fibroblasts and in model cell lines.
4. To compare the expression the ATAD3C protein with that of the other two proteins (ATAD3A and B) coded in the same gene locus. ATAD3B and C were generated by genetic duplication of ATAD3A during evolution. We will study them in both the patient’s fibroblasts and in cell models with different states of OxPhos activity.
5. To use metabolomics to study the patient’s plasma and cerebrospinal fluid in order to obtain more information about the metabolic processes affected.
6. To analyze the expression of the MAGIX gene and of the corresponding protein in the patient’s fibroblasts and in control fibroblasts.

Project expenses

For this project, the research group already has experienced staff members to carry out the experiments. Funding will be required for consumables and to pay for external services, such as sequencing, proteomics and microscopy.
We will therefore require 30,000€ per year over a three-year period.
Details of the expenses are as follows:



Disposable glassware and plasticware. 1500

General reagents. 1500

Reagents for the culture of eukaryotic cells (culture media, bovine fetal serum, antibiotics, transfection reagents, etc.) 4000

Kits for different uses (cloning of PCR products, extraction of bacterial plasmids, DNA purification, RNA extraction, cDNA synthesis, etc.) 9000

Molecular biology reagents (oligonucleotides, Taq polymerase, plasmids, restriction enzymes, ligase enzyme, antibodies, etc.) 10000

Service expenses:

Service charges for using external services: DNA sequencing, proteomic analysis and microscopy service. 4000



Execution: 100%