Biomedical subjects

Philippe A Parone

Publications and source records attributed to Philippe A Parone.

4 recordsLinked to original sources

PubMed2006

Mitochondrial fission and apoptosis: an ongoing trial.

Apoptosis is a form of programmed cell death that is essential for the development and tissue homeostasis in all metazoan animals. Mitochondria play a critical role during apoptosis, since the release of pro-apoptogenic proteins from the organelle is a pivotal event in cell death triggered by many cytotoxic stimuli. A striking morphological change occurring during apoptosis is the disintegration of the semi-reticular mitochondrial network into small punctiform organelles. It is only recently that this event has been shown to require the activity of proteins involved in the physiological processes of mitochondrial fission and fusion. Here, we discuss how this mitochondrial morphological transition occurs during cell death and the role that it may have in apoptosis.

Animals↗

PubMed2006

Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent apoptosis.

Apoptosis, induced by a number of death stimuli, is associated with a fragmentation of the mitochondrial network. These morphological changes in mitochondria have been shown to require proteins, such as Drp1 or hFis1, which are involved in regulating the fission of mitochondria. However, the precise role of mitochondrial fission during apoptosis remains elusive. Here we report that inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down-regulating of Drp1 or hFis1, prevents the fragmentation of the mitochondrial network and partially inhibits the release of cytochrome c from the mitochondria but fails to block the efflux of Smac/DIABLO. In addition, preventing mitochondrial fragmentation does not inhibit cell death induced by Bax/Bak-dependent death stimuli, in contrast to the effects of Bcl-xL or caspase inhibition. Therefore, the fission of mitochondria is a dispensable event in Bax/Bak-dependent apoptosis.

Animals↗

PubMed2005

Building the mitochondrial proteome.

Mitochondria are essential organelles for cellular homeostasis. A variety of pathologies including cancer, myopathies, diabetes, obesity, aging and neurodegenerative diseases are linked to mitochondrial dysfunction. Therefore, mapping the different components of mitochondria is of particular interest to gain further understanding of such diseases. In recent years, proteomics-based approaches have been developed in attempts to determine the complete set of mitochondrial proteins in yeast, plants and mammals. In addition, proteomics-based methods have been applied not only to the analysis of protein function in the organelle, but also to identify biomarkers for diagnosis and therapeutic targets of specific pathologies associated with mitochondria. Altogether, it is becoming clear that proteomics is a powerful tool not only to identify currently unknown components of the mitochondrion, but also to study the different roles of the organelle in cellular homeostasis.

Animals↗

PubMed2003

hFis1, a novel component of the mammalian mitochondrial fission machinery.

The balance between the fission and fusion mechanisms regulate the morphology of mitochondria. In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission. This event was inhibited by a dominant negative mutant of Drp1 (Drp1(K38A)), a major component of the fission apparatus. Fragmentation of the mitochondrial network by hFis1 was followed by the release of cytochrome c and ultimately apoptosis. Bcl-xL was able to block cytochrome c release and apoptosis but failed to prevent mitochondrial fragmentation. Our studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.

Amino Acid Sequence↗