A5021776423- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Nerve injury and regeneration
- Ubiquitin and proteasome pathways
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Trace Elements in Health
- Endoplasmic Reticulum Stress and Disease
- Diet and metabolism studies
- Cancer-related Molecular Pathways
- Ion channel regulation and function
- Alzheimer's disease research and treatments
- Virus-based gene therapy research
- interferon and immune responses
- Sphingolipid Metabolism and Signaling
- Retinal Development and Disorders
University of Geneva
2015-2024
Adc Therapeutics (Switzerland)
2024
Université de Montpellier
2016
National Institutes of Health
2011
National Institute of Neurological Disorders and Stroke
2011
University of Zurich
2009
The University of Melbourne
2009
Health Sciences Centre
2003
McMaster University
2003
Merck Serono (Switzerland)
2000-2001
Here we report that in staurosporine-induced apoptosis of HeLa cells, Bid, a BH3 domain containing protein, translocates from the cytosol to mitochondria. This event is associated with change conformation Bax which leads unmasking its NH2-terminal and accompanied by release cytochrome c A similar finding reported for cerebellar granule cells undergoing induced serum potassium deprivation. The Bax-conformational prevented Bcl-2 Bcl-xL but not caspase inhibitors. Using isolated mitochondria...
AbstractIn many types of apoptosis, the proapoptotic protein Bax undergoes a change in conformation at level mitochondria. This event always precedes release mitochondrial cytochrome c, which, cytosol, activates caspases through binding to Apaf-1. The mechanisms by which triggers c are unknown. Here we show that following BH3-domain-only Bid, oligomerizes and then integrates outer membrane, where it cytochromec release. membrane insertion triggered Bid may represent key step pathways leading...
Proteins of the Bcl-2 family are intracellular membrane-associated proteins that regulate programmed cell death (apoptosis) either positively or negatively by as yet unknown mechanisms. Bax, a pro-apoptotic member family, was shown to form channels in lipid membranes. Bax triggered release liposome-encapsulated carboxyfluorescein at both neutral and acidic pH. At physiological pH, could be blocked Bcl-2. Bcl-2, contrast, pH only. In planar bilayers, formed pH- voltage-dependent...
Although mixed lineage kinase domain-like (MLKL) protein has emerged as a specific and crucial for necroptosis induction, how MLKL transduces the death signal remains poorly understood. Here, we demonstrate that full four-helical bundle domain (4HBD) in N-terminal region of is required sufficient to induce its oligomerization trigger cell death. Moreover, found patch positively charged amino acids on surface 4HBD binds phosphatidylinositol phosphates (PIPs) allows recruitment plasma...
Approximately half of the neurons produced during embryogenesis normally die before adulthood. Although target-derived neurotrophic factors are known to be major determinants programmed cell death—apoptosis—the molecular mechanisms by which trophic interfere with death regulation largely unknown. Overexpression bcl-2 proto-oncogene in cultured sympathetic has now been shown prevent apoptosis induced deprivation nerve growth factor. This finding, together previous demonstration expression...
The transport of pyruvate, the end product glycolysis, into mitochondria is an essential process that provides organelle with a major oxidative fuel. Although existence specific mitochondrial pyruvate carrier (MPC) has been anticipated, its molecular identity remained unknown. We report MPC heterocomplex formed by two members family previously uncharacterized membrane proteins are conserved from yeast to mammals. Members were found in inner membrane, and mutants lacking showed severe defects...
Bax is a Bcl-2 family protein with proapoptotic activity, which has been shown to trigger cytochrome crelease from mitochondria both in vitro and vivo. In control HeLa cells, present the cytosol weakly associated as monomer an apparent molecular mass of 20,000 Da. After treatment cells apoptosis inducer staurosporine or UV irradiation, two large weight oligomers/complexes 96,000 260,000 Da, are integrated into mitochondrial membrane. prevents oligomerization insertion The outer membrane...
Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is pore-forming, mitochondria-associated protein whose mechanism of action still unknown. During apoptosis, cytochrome C released from the mitochondria into cytosol where it binds to APAF-1, mammalian homologue Ced-4, and participates in activation caspases. The release has been postulated be consequence opening mitochondrial permeability transition pore (PTP). We now report that Bax...
Bax is a Bcl-2-family protein with pro-apoptotic activity that can form channels in lipid membranes. The has been shown to trigger cytochrome c release from mitochondria both vitro and vivo. Recombinant human isolated the presence of detergent was found be present as an oligomer apparent molecular mass approx. 160000 Da on gel filtration. When absence purified monomeric 22000 Da. oligomers formed liposomes triggered mitochondria, whereas inactive respects. Incubation 2% octyl glucoside...
The balance between the fission and fusion mechanisms regulate morphology of mitochondria. In this study we have identified a mammalian protein that call hFis1, which is orthologue yeast Fis1p known to participate in mitochondrial division. when overexpressed various cell types, localized outer membrane induced fission. This event was inhibited by dominant negative mutant Drp1 (Drp1(K38A)), major component apparatus. Fragmentation network hFis1 followed release cytochrome c ultimately...
Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1, whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria induces OPA1 processing and results in mitochondrial fragmentation, allowing selective removal damaged mitochondria. In this study, we demonstrate that two classes metallopeptidases regulate cleavage inner membrane: isoenzymes adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities...
We have studied the phosphorylation of Bcl-2 family proteins by different mitogen-activated protein (MAP) kinases. Purified was found to be phosphorylated c-Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) p54-SAPKβ, and this is specific insofar as extracellular signal-regulated 1 (ERK1) p38/RK/CSBP (p38) catalyzed only weak modification. undergoes similar in COS-7 when coexpressed together with p54-SAPKβ constitutive Rac1 mutant G12V. This seen both 32PO4labeling appearance five...
Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, role mitochondrial in homeostasis organelle still unknown. Here we report that preventing fission, down-regulating expression Drp1 mammalian cells leads to loss DNA decrease respiration coupled an increase levels cellular reactive oxygen species (ROS). At level, dysfunction resulting from lack drop ATP, inhibition cell proliferation autophagy. In...