Cell death mitochondria

Loeffler, M., and Kroemer, G., 2000, The mitochondrion in cell death control certainties and incognita, Etp. CellRes. 256 19-26. 

We directed our initial attention to the mitochondrion-specific phospholipid, cardiolipin because it is particularly rich in polyunsaturated fatty acids which are vulnerable to oxidative attack. It seemed reasonable to speculate that mitochondrial cardiolipin may degrade by the enhanced peroxidation reactions during apoptotic cell death,... 

As the power house of the cell, the mitochondrion is essential for energy metabolism. As the motor of cell death (1), this organelle is central to the initiation and regulation of apoptosis. In addition, mitochondria are critically involved in the modulation of intracellular calcium concentration and the mitochondrial respiratory chain is the major source of damaging reactive oxygen species. Mitochondria also play a crucial role in numerous catabolic and anabolic cellular pathways. 

Various aspects of myocardial ischemia are highlighted in Chapter 1. Reperfusion, generally a pre-requisite for tissue survival may increase injury over and above that sustained during ischemia. In this context, the role of apoptosis is appreciated. Mitochondrion seems to be the site of life or death . This organelle that provides ATP to sustain cell life is converted to an instrument of programmed cell death or necrosis upon stress depending on the severity of the insult. 

Botelho MV, Capela J, Soares P, et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer. 2005 92 1817-1818. 

Mitochondria and cell death Although oxidative phosphorylation is a mitochondrial process, most ATP utilization occurs outside of the mitochondrion. ATP synthesized from oxidative phosphorylation is actively transported from the matrix to the intermembrane space by adenine nucleotide translocase (ANT). Porins form voltage-dependent anion channels (VDAC) through the outer mitochondrial membrane for the diffusion of H2O, ATP metabolites, and other ions. Under certain types of stress, ANT, VDAC, and other proteins form a nonspecific open channel known as the mitochondrial permeability transition pore. This pore is associated with events that lead rapidly to necrotic cell death. 

Borutaite V, Brown GC (1996) Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide. Biochem J 315 295-299 Boya P, Andreau K, Poncet D, Zamzami N, Perfettini JL, Metivier D, OJcius DM, Jaattela M, Kroemer G (2003a) Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med 197 1323-1334 Boya P, Gonzalez-Polo RA, Poncet D, Andreau K, Vieira HLA, Roumier T, Perfettini JL, Kroemer G (2003b) Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene 22 3927-3936 Bravo JF, Jacobson MP, Mertens BF (1997) Fatty liver and pleural effusion with ibuprofen therapy. Ann Intern Med 87 200-201... 

Chloramphenicol blocks translation of mRNA in bacteria by inhibiting the peptidyl transferase of the large ribosomal subunit. It does not interfere with the peptidyl transferase in the large subunit of eukaryotic ribosomes. However, the mitochondrion of animal cells contains ribosomes that are similar to bacterial ribosomes, and chloramphenicol blocks protein synthesis in this organelle. This may cause side effects in humans, such as deafness due to cell death in the acoustic nerves from a lack of ATP supply in them. 

Loeffler M, Kroemer G. The mitochondrion in cell death control Certainties and incognita. Exp Cell Res 2000 256(l) 19-26. 

Using a novel strategy in which bacterial sphingomyelinase was targeted and expressed in different subcellular compartments, Birbes et al. demonstrated that only ceramide generated in the mitochondrion was capable of inducing apoptotic cell death (Birbes et al., 2001). 

In this model, cellular stress mediates the release of cytochrome C from the mitochondrion. The proapoptotic proteins Bax and BH3 proteins support the release of cytochrome C, while the antiapoptotic Bcl2 protein has an inhibitory effect. Cytosolic cytochrome C binds to the cofactor Apaf 1, which then associates via its CARD motif with procaspase 9 to a complex termed apopto-some. In this complex, procaspase 9 is processed to the mature caspase which subsequently activates downstream effector caspases and commits the cell to death. 

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