1995 M.S. in Neurosciences Universities of Bordeaux 1 and 2, France
1996 M.S. in Biochemistry University of Bordeaux 2, France
2000 PhD University of Bordeaux 2, France
2001-02 Postdoctoral Fellow University of Barcelona, Spain (Biochemistry & cell biology)
2002-06 Postdoctoral Fellow NYU College of Dentistry (Biochemistry & cell biology)

Mitochondria are organelles involved in both life and death processes within all eukaryotic cells. They are crucial elements in energy production as they host multiple enzymes of intermediate metabolism and oxidative phosphorylation. Mitochondria also play a pivotal role in the response of many cell types to signals generated by the apoptotic cascade, signals which lead to programmed cell death, i.e., apoptosis. The Bcl-2 family of proteins is a key regulator of the mitochondrial response to apoptotic signals and this family contains both pro- and anti-apoptotic members. Many of these proteins eventually localize to mitochondria and finely regulate the process of apoptosis by controlling the release of mediators of the apoptotic program such as cytochrome c. At this point however, the mechanisms that underlie the action of Bcl-2 family members in mitochondria have yet to be resolved. Nevertheless, it is important to better understand these mechanisms as apoptosis is a phenomenon fundamental to eukaryotes and is related to both physiological (e.g. tissue homeostasis and organogenesis) and pathophysiological (e.g. cancer and neurodegenerative diseases) situations. A channel called the Mitochondrial Apoptosis-induced Channel, or MAC, forms in the outer membrane of mitochondria early in apoptosis. Importantly, MAC is the putative cytochrome c release channel and MAC formation occurs when Bax translocates to these organelles. Bax is a pro-apoptotic member of the Bcl-2 family of proteins, a family that exquisitely regulates apoptosis. However, genetic inactivation of Bax is not sufficient to rescue cells from apoptosis, abolish cytochrome c release, or prevent MAC formation. These results indicate that other mitochondrial proteins likely participate in the formation and activity of MAC.

My research interests mainly concern the study of how the pro-apoptotic proteins Bax and Bak regulate MAC formation during the early steps of apoptosis. As Bax was shown to be a MAC component, one part of this study is to understand the molecular mechanisms by which this protein is inserted and activated to form MAC in the mitochondrial outer membrane. Another part is to identify novel Bax partners in MAC formation using a co-immunoprecipitation approach coupled to mass spectrometry. This last aspect could allow a better knowledge in both MAC structure and function; two fundamental aspects of a better pharmacological profiling of this death channel.

Dejean, L., Beauvoit, B., Guerin, B., Rigoulet, M. (2000) Growth of the yeast Saccharomyces cerevisiae on a non-fermentable substrate :control of energetic yield by the amount of mitochondria. Biochim. Biophys. Acta 1457:45-56.

Dejean, L., Beauvoit, B., Bunoust, O., Fleury, C., Guerin, B., Rigoulet, M. (2001) The calorimetric-respirometric ratio is an on-line marker of enthalpy efficiency of yeast cells growing on a non-fermentable carbon source. Biochim. Biophys. Acta 1503:329-340.

Dejean, L., Beauvoit, B., Bunoust, O., Guerin, B., Rigoulet, M. (2002) Activation of Ras cascade increases the mitochondrial enzyme content of respiratory competent yeast. Biochem. Biophys. Res. Commun. 293:1383-1388.

Dejean, L., Beauvoit, B., Alonso, A.P., Bunoust, O., Guerin, B., Rigoulet, M. (2002) cAMP-induced modulation of the growth yield of Saccharomyces cerevisiae during respiratory and respiro-fermetative metabolism. Biochim. Biophys. Acta 1554:159-169.

Dejean, L., Bunoust, O., Schaeffer, J., Guerin, B., Rigoulet, M., Beauvoit, B (2002). Control of growth yield of yeast on respiratory substrate by mitochondrial content. Thermochim. Acta 394:113-121.

Devin, A., Dejean, L., Beauvoit, B., Chevtzoff, C., Averet, N., Bunoust, O., Rigoulet, M. (2006) Growth yield homeostasis in respiring yeast is due to a strict mitochondrial content adjustment. J. Biol. Chem. 281:26779-26784.

Sartor, P., Madec, F., Garcia, L., Dejean, L., Beauvoit, B., Dufy, B., Rigoulet, M. (2004) Interactions between intracellular chloride concentrations, intracellular pH and energetic status in rat lactotrope cells in primary culture. Gen. Physiol. Biophys. 23:195-208.

Dejean, L., Camara, Y., Sibille, B., Solanes, G., Villarroya, F. (2004) Uncoupling protein-3 sensitizes cells to mitochondrial-dependent stimulus of apoptosis. J. Cell. Physiol. 201:294-304.

Guo, L., Pietkiewicz, D., Pavlov, E.V., Grigoriev, S.M., Kasianowicz, J.J., Dejean, L.M., Korsmeyer, S.J., Antonsson, B., Kinnally, K.W. (2004) Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC. Am. J. Physiol. Cell Physiol. 286:C1109-1117.

Martinez-Caballero, S., Dejean, L.M., Kinnally, K.W. (2004) Some amphiphilic cations block the mitochondrial apoptosis-induced channel, MAC. FEBS Lett. 568:35-38.

Grigoriev, S.M., Muro, C., Dejean, L.M., Campo, M.L., Martinez-Caballero, S., Kinnally, K.W. (2004) Electrophysiological approaches to the study of protein translocation in mitochondria. Int. Rev. Cytol. 238:227-274.

Dejean, L.M., Martinez-Caballero, S., Guo, L., Hughes, C., Teijido, O., Ducret, T., Ichas, F., Korsmeyer, S.J., Antonsson, B., Jonas, E.A., Kinnally, K.W. (2005) Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Mol. Biol. Cell 16:2424-2432.

Martinez-Caballero, S., Dejean, L.M., Jonas E.A., Kinnally, K.W. (2005) The role of mitochondrial apoptosis induced channel MAC in cytochrome c release. J. Bioenerg. Biomembr. 37:155-164.

Chinopoulos, C., Starkov, A.A., Grigoriev, S., Dejean, L.M., Kinnally, K.W., Liu, X., Ambudkar, I.S., Fiskum, G. (2005) Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca(2+). J. Bioenerg. Biomembr. 37:237-247.

Pavlov, E., Grigoriev, S.M., Dejean, L.M., Zweihorn, C.L., Mannella, C.A., Kinnally, K.W. (2005) The mitochondrial channel VDAC has a cation-selective open state. Biochim. Biophys. Acta 1710:96-102.

Dejean, L.M., Martinez-Caballero, S., Manon, S., Kinnally, K.W. (2006) Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins. Biochim. Biophys. Acta 1762:191-201.

Dejean, L.M., Martinez-Caballero, S., Kinnally, K.W. (2006) Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis ?. Cell Death Differ. 13:1387-1395.

Kinnally, K.W., Martinez-Caballero, S., Dejean, L.M. (2006) Detection of MAC, the mitochondrial apoptosis induced channel, and its regulation by Bcl-2 family proteins. Current Protocols in Toxicology, Unit 2.12 Sup 30, 2.12.1-2.12-34.