Conferences
2015
Conférence GIRC
Grenoble Institute for Cancer Research
.
Tuesday 3 March
Nazanine Modjtahedi
Gustave Roussy cancer center, Villejuif
IAB Conference room 11 am
A strategy for the correction of the mitochondrial
respiratory chain complex I deficiency
Mitochondrial diseases, also called « mitochondriopathies », gather a vast number of
heterogeneous diseases with a large spectrum of organ-specific manifestations that primarily
affect infants and are essentially due to an inborn or progressive dysfunction of mitochondrial
oxidative phosphorylation. These genetically transmitted illnesses that have an incidence
below 1/10 000 are caused by mutations in either mitochondrial or nuclear-encoded genes that
are crucial for the structure, function or regulation of the five multiprotein complexes (CI to
CV) that form the mitochondrial respiratory chain machinery. Although a large number of
mutations that are responsible for mitochondriopathies have been described, more must be
identified because their characterization will be essential for molecular diagnostics, genetic
counseling, understanding of the molecular pathogenesis of these diseases, as well as the
proposal of therapeutic strategies.
The current state of the art reveals that mutations in the nuclear-encoded mitochondrial
protein AIF (Apoptosis Inducing Factor) account for X-linked severe mitochondriopathies in
humans. The mitochondrial activity of AIF is required for the optimal function of the
respiratory chain, and its tissue-specific loss causes a mitochondriopathy that is accompanied
by a reduction in the relative abundance of the protein subunits of complex I (CI), which is
the most affected one. Hypomorphic or deletion mutant mouse models of Aif have led to the
generation of the first faithful and reliable animal model of complex I deficiency, which is
responsible for about 30% of human mitochondrial diseases.
Here, we will first discuss the identification of the first mitochondrial partner of AIF that
explains how AIF contributes to the biogenesis of respiratory chain complexes and then
present a strategy to correct the complex I deficiency that is caused by the downregulation or
total loss of AIF.
Invited by Saadi Khochbin
Grenoble Institut Recherche Cancer : Institut Albert Bonniot, Institut de Recherches en
Technologies et Sciences pour le
Vivant, Institut de Biologie Structurale, Grenoble Institut Neurosciences
Rond Point de La Chantourne, 38700 La Tronche (tram line B, stop: Grand Sablon)
The seminar is followed by discussions and exchanges with the speaker and a sandwich buffet is offered.
http://www-iab.ujf-grenoble.fr