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MITOCHONDRIAL FAILURE IN CELL TRANSFORMATION

For many years mitochondria have been implicated in the process of carcinogenesis. At the beginning of 20th century Otto Warburg has started research focused on failure of oxadative metabolism in cancer cells. In his work he described disruption of respiration as typical for cancer cells. Warburgs discovery resulted in establishment of many projects focused on the role of mitochondria in cell transformation. Since that time multiple reasearch groups have reported mitochondria DNA mutations in majority types of cancer.

APOPTOSIS – TARGETED ANTICANCER THERAPY

Apoptosis is the major form of cell suicide. Most conventional anticancer agents induce apoptosis indirectly. Although chemiotherapeutic drugs should selectively kill only tumor cells, normal cells are often susceptible to cytotoxic or cytostatic effects of these agents. This is a reason of potentially harmful side effects including inflammation and damage to the surrounding normal tissue. A new therapeu- tic approach in cancer treatment is the use of substances that stimulate cytokine production, angiogenesis inhibitors, gene therapies, antisense oligonucleotides and monoclonal antibodies.

THE TOB/SAM COMPLEX: AN ESSENTIAL FUNCTION IN MITOCHONDRIA BIOGENESIS

β-barrel proteins are present in the outer membrane of Gram-negative bacteria and of organel- les of endosymbiotic origin, i.e. mitochondria and chloroplasts where they perform a variety of functions. Mitochondrial β-barrel proteins are important for protein import, metabolite transport and the organelle morphology and distribution. They also seem to play a crucial role in mitochondria evolution. Quite recently a specific pathway for the insertion of β-barrel proteins was identified in both mitochondria and Gram-negative bacteria and was proved to be conserved during evolution.

MITOCHONDRIA - AN APOPTOSIS INTEGRATORS

Supernumerary, old or damaged cells of multicellular organisms are eliminated by apoptosis – programmed cell death. Apoptosis is accompanied by series of characteristic morphological and biochemi- cal events. The cell activates a cascade of cysteine proteases – caspases, that digest target proteins. Nucleases are also activated, which together leads to irreversible cell damage within few hours. Mitochon- dria are the cell compartment that integrates signals from different apoptotic pathways activated by ischemia, heat shock or growth hormones depletion.

PLANT DYNAMIN-LIKE PROTEINS – INSIGHTS INTO THE EVOLUTION OF DIVISION MACHINERY OF MITOCHONDRIA AND PLASTIDS

Dynamin and dynamin-related proteins (DRP) participate in many processes essential for normal function of the cells and organisms. They were found both in animals and plants. In Arabidopsis thaliana 16 different dynamin-related proteins were identified that are grouped into six subfamilies. DRP1 and soybean fragmoplastin participate in the cell plate formation during cytokinesis. Two mem- bers of DRP2 subfamily display domain structure similar to mammalian classical dynamins and may be involved in endocytosis and membrane recycling via clathrin-coated vesicles.

PLANT DYNAMIN-LIKE PROTEINS – INSIGHTS INTO THE EVOLUTION OF DIVISION MACHINERY OF MITOCHONDRIA AND PLASTIDS

Dynamin and dynamin-related proteins (DRP) participate in many processes essential for normal function of the cells and organisms. They were found both in animals and plants. In Arabidopsis thaliana 16 different dynamin-related proteins were identified that are grouped into six subfamilies. DRP1 and soybean fragmoplastin participate in the cell plate formation during cytokinesis. Two mem- bers of DRP2 subfamily display domain structure similar to mammalian classical dynamins and may be involved in endocytosis and membrane recycling via clathrin-coated vesicles.

TRANSLOCATION OF SIGNALING PROTEINS IS AN ELEMENT OF THE DELAYED POSTISCHEMIC NEURONAL CELL DEATH

Neuronal degeneration following transient global cerebral ischaemia develops from complex series of pathophysiological events that evolve in time and intracellular space. During both, the early and delayed, postischemic stages translocation of proteins to postsynaptic density (PSD) and mitochon- dria are probably associated with recovery or cell death in vulnerable brain regions. Early after the insult a significant increase in the amount of CamKII and PKC isoforms is observed in PSD.

Morphology and function of the mitochondria of sperm and male fertility. Part II.Zaburzenia morphological and functional mitochondrial inserts sperm

Morphological and functional disorders inserts sperm mitochondria , which are more often the cause of male infertility ( astenoteratozoospermii ) can be identified using a precise diagnosis of mitochondrial insert sperm .

Morphology and function of the mitochondria of sperm and male fertility. Part I. Normal morphology and function inserts the sperm

Sperm Mitochondria are structures unique and slightly different from somatic mitochondria . They undergo a series of morphological , biochemical and molecular changes associated with the expression of specific structural and enzymatic proteins , which are markers of maturation during spermatogenesis. These include , among others, gonadalny cytochrome cT , LDH - C4, sulfhydryl oxidase , protease LON and hsp60 . Activin A secreted by Sertoli cells when spermiogenezy mitochondria induces morphological changes spermatids , leading to the formation of condensed structures of these organelles.

Kinetics and regulation of Smac / DIABLO release from the mitochondria of cancer cells upon stimulation Apoptogenic

Most of the currently used anticancer drugs and radiotherapy induces apoptosis by DNA damage or inhibition of key enzymes involved in cell survival signaling pathways . This triggers a cascade of reactions leading to the activation of pro-apoptotic proteins Bcl- 2 family , such as Bad , Bid , Bax or Bak , forming a specific channel or coformation of megachannels ( mPTP ) in the outer mitochondrial membrane , allow the release of apoptogenic proteins , such as cytochrome c , Smac / DIABLO , AIF , Omi/HtrA2 , procaspase 9 and 3 and endonuclease G.

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The Editorial Board
Andrzej Łukaszyk - przewodniczący, Zofia Bielańska-Osuchowska, Szczepan Biliński, Mieczysław Chorąży, Aleksander Koj, Włodzimierz Korochoda, Leszek Kuźnicki, Aleksandra Stojałowska, Lech Wojtczak

Editorial address:
Katedra i Zakład Histologii i Embriologii Uniwersytetu Medycznego w Poznaniu, ul. Święcickiego 6, 60-781 Poznań, tel. +48 61 8546453, fax. +48 61 8546440, email: mnowicki@ump.edu.pl

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