Apoptosis mitochondria

X.M. Yin, Signal transduction mediated by Bid, a pro-death Bcl-2 family protein, connects the death receptor and mitochondria apoptosis pathway. Cell Res. 10, 161-167 (2000). 

Vladimirov YuA (2002) Breach of barrier properties for internal and external mitochondrion membranes, necrosis and apoptosis. Russian Biol Membr. 19 356-377. 

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. 

The oxidative phosphorylation system contains over 80 polypeptides. Only 13 of them are encoded by mtDNA, which is contained within mitochondria, and all the other proteins that reside in the mitochondrion are nuclear gene products. Mitochondria depend on nuclear genes for the synthesis and assembly of the enzymes for mtDNA replication, transcription, translation, and repair (Tl). The proteins involved in heme synthesis, substrate oxidation by TCA cycle, degradation of fatty acids by /i-oxidalion, part of the urea cycle, and regulation of apoptosis that occurs in mitochondria are all made by the genes in nuclear DNA. 

Mitochondria release not only cytochrome c but also many pro-apoptotic factors (Table 17.1). They are normally localized in the intermembrane space of mitochondria. However, except for cytochrome c and the apoptosis inducing factor (AIF), their functions in the mitochondria have not been determined or they may have no function under normal conditions. Because they are larger than 5kD, they remain inside the mitochondrion. Once the mitochondrial outer membrane is permeabi-... 

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. 

In mammals, mercury is generally immunosuppressive, and apoptosis has been suggested as a possible mechanism for immunosuppression. Apoptosis may be induced in human CD4+ T cells at concentrations as low as 0.5 /xM HgCl2 (ref. 114), comparable to the results with lake trout thymocytes75. The target organelle for this apoptotic effect in human T cells is the mitochondrion, and the induction of oxidative... 

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... 

Mitochondrion-selective reagents for assessment of mitochondrial activity, localization and abundance, monitoring effects of pharmacological agents, such as anesthetics that alter mitochondrial function. Important role in apoptosis... 

Fig. 6. Summary of antiviral host responses and Ad countermeasures. The figure is discussed in the text. Adenovirus proteins with known immunomodulatory functions are shaded black the El A activity triggering apoptosis is depicted in gray. For simplicity, potential effects of E1B/19K on Fas-, TRAIL-, and TNF-mediated apoptosis/cytolysis that are controversial are omitted. Also, potential stimulatory or inhibitory effects of 14.7K on NF-kB signaling is not indicated. Trimers of TNF, FasL, and TRAIL exist as membrane-bound and secreted forms. Abbreviations AfO, macrophages Ahs. antibodies PM. plasma membrane (7, Golgi M, mitochondrion...

The HjOj is a freely diffusible species that can cross membranes. Hence, mitochondria have two major sources of HjO On the one hand, generated by disproportionation of superoxide anion in the mitochondrial membrane and, on the other hand, the oxidative deamination of biogenic amines by the outer mitochondrial membrane-bound monoamine oxidase activity. Mitochondrion-generated is involved in the redox regulation of cell signaling pathways. The steady-state levels of ([HjOJss) determine the cellular redox status and the transition from proliferation to apoptosis and necrosis. 

Figure 3.22 Mitochondrial-mediated apoptotic signaling. Cyt c release from the mitochondrion leads to formation of the apoptosome and activation of procaspase-9. Active caspase-9 cleaves and activates caspase-3, which ieads to apoptosis.

Metivier, D. Dallaporta, B. Zamzami, N. Larochette, N. Susin, S. A. Marzo, L Kroemer, G. Cytofluorometric detection of mitochondrial alterations in early CD95/Fas/APO-l triggered apoptosis of Jurkat T lymphoma cells. Comparison of seven mitochondrion-specific fluorochromes. Immunol. Lett. 1998,61,157-163. 

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