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Mitochondria are dynamic organelles whose homeostasis is defined by two opposite processes: fission (or fragmentation), or fusion. Fission of mitochondria results in generation of smaller organelles and fusion is when they produce tubular or net-like structures. Although a number of proteins are already known to control the process of fission/fusion additional regulators controlling these processes are being found. The Bcl-2 family members take part in the regulation of apoptosis and according to the current view are involved in the mitochondrial net-like structure maintenance. In this review we will discuss mechanisms of mitochondrial fission/fusion regulation and summarize the available information on the role of Bcl-2 family members in the regulation of mitochondrial fission/fusion dynamics.

The predominant definition of apoptosis considers that the elimination of the apoptosing cell is by heterolytic degradation following phagocytosis by an assisting scavenger (efferocytosis). However, an alternative and largely underestimated outcome of apoptosis is secondary necrosis, an autolytic process of cell disintegration with release of cell components that occurs when there is no intervention of scavengers and the full apoptotic program is completed. Secondary necrosis is the typical outcome of apoptosis in unicellular eukaryotes but, importantly, it may also occur in multicellular animals and has been implicated in the genesis of important human pathologies. Secondary necrosis is a mode of cell elimination with specific molecular and morphological features and should be considered the natural outcome of the complete apoptotic program., (Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

A cell line of the ameba assigned to the genus Acanthamoeba by morphological and cariotypic signs and by the specific features of its life cycle was isolated from the thymus of a child operated on for heart disease. The line received the name CDHT (Cells Derived from Human Thymus). Actively proliferating mammalian cells maintain the multiplication of Acanthamoeba cells in vitro. Using thymocytes as an example, it was shown that death of these cells occurred through the mechanism of apoptosis. The human thymocytes preincubated with the supernatant obtained through the cocultivation of CDHT and thymocytes may also undergo apoptosis.

The number of cells in an organism is determined by regulating both cell proliferation and cell death. Relatively few mechanisms have been identified that can modulate both of these processes. In a screen for Drosophila mutations that result in tissue overgrowth, we identified salvador (sav), a gene that promotes both cell cycle exit and cell death. Elevated Cyclin E and DIAP1 levels are found in mutant cells, resulting in delayed cell cycle exit and impaired apoptosis. Salvador contains two WW domains and binds to the Warts (or LATS) protein kinase. The human ortholog of salvador (hWW45) is mutated in three cancer cell lines. Thus, salvador restricts cell numbers in vivo by functioning as a dual regulator of cell proliferation and apoptosis.

Hyperthermia (HT) is a physiological agent able to induce apoptosis in normal and tumor cells. The ability of HT to damage different cellular components is underlying the mechanism of apoptogenic activity of HT. The review is aimed to consider the studies representing mainly HT production of genotoxic initial signal and pathways of its transduction to programmed cytotoxic event or apoptosis. In this regard we analyse the membrane effect of HT, HT-induced chromatin and nuclear matrix structure changes, DNA damage, effect of HT on DNA-repair mechanism, and the role of heat shock proteins in apoptosis and cancerogenesis.

A marked feature of eukaryotic programmed cell death is an early drop in mitochondrial transmembrane potential. This results from the opening of permeability transition pores, which are composed of adenine nucleotide translocators and mitochondrial porins. The latter share striking similarities with bacterial porins, including down-regulation of their pore size by purine nucleotides), suggesting a common origin. The porins of some invasive bacteria play a crucial role during their accommodation inside the host cell and this coexistence resembles the endosymbiotic origin of mitochondria. The above observations suggest that early in eukaryotic evolution, former invaders may have used porin-type channels to enter their host and to induce its death when the levels of its cytoplasmic purine nucleotides were dropped. The appearance of adenosine nucleotide translocators in the primitive eukaryotes, which permitted usage of the oxidative metabolism of the invaders, provided the basis for the permeability transition phenomena, now linked to the apoptotic process. Bcl-2-type molecules, being able to modulate the permeability transition pores by interaction with adenosine nucleotide translocators, may have played an essential role in conferring a means of controlling apoptosis.