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A cornucopia of human pathologies, including several for which no efficient therapy is currently available, exhibit impaired apoptosis. The description of the multiple signaling pathways leading to apoptosis and the [...]

I. Introduction II. An Overview of Cell Death Pathways A. Apoptosis B. Autophagic cell death C. Necrosis D. Mitotic catastrophe III. Detection of Mitochondrial Membrane Permeabilization A. Signs of outer [...]

Replication of human cytomegalovirus (CMV) requires the expression of the viral mitochondrialocalized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by recruiting Bax to mitochondria, resulting in its neutralization. We show that vMIA decreases cell size, reduces actin polymerization, and induces cell rounding. As compared with vMIA-expressing CMV, vMIA-deficient CMV, which replicates in fibroblasts expressing the adenoviral apoptosis suppressor E1B19K, induces less cytopathic effects. These vMIA effects can be separated from its cell death-inhibitory function because vMIA modulates cellular morphology in Bax-deficient cells. Expression of vMIA coincided with a reduction in the cellular adenosine triphosphate (ATP) level, vMIA selectively inhibited one component of the ATP synthasome, namely, the mitochondrial phosphate carrier. Exposure of cells to inhibitors of oxidative phosphorylation produced similar effects, such as an ATP level reduced by 30%, smaller cell size, and deficient actin polymerization. Similarly, knockdown of the phosphate carrier reduced cell size. Our data suggest that the cytopathic effect of CMV can be explained by vMIA effects on mitochondrial bioenergetics.

The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nudeotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death., Pro- and antiapoptotic members of the Bcl-2 family have pleiotropic effects on caspase activation cascades regulated by the apoptosome, on cellular redox potentials, and on the barrier function of mitochondrial [...]

Transmission electron microscopy revealed the presence of a 11- to 30-nm capsular material surrounding Mycoplasma penetrans. Staining studies suggest that this capsular material is composed of polysaccharides and anchored to the plasma membrane by polypeptides. Electrophoretic analysis revealed the presence of high- and low-molecular mass glycosylated materials in the capsule with different heat and enzyme sensitivities.

The mitochondrion, the cell's Pandora's box, contains potentially harmful proteins that it keeps hidden away. Activation of these harmful proteins sets in motion programmed cell death (apoptosis) pathways that result [...]