title: What of apoptosis is important: the decay process or the causative origin?
abstract: Apoptosis is defined as the process of ''programmed cell death'' (PCD), during which many cells simultaneously die from within along a very orderly pattern. PCD is as intrinsic for cells as mitosis and is involved in both degenerative and developmental processes of organs and organisms. The pattern of apoptotic cell decay is caused by the total cellular content. Since all body cells possess the same genome, they are similar in many aspects and, therefore, the major processes are nearly identical in all cell types. The same destructive processes also occur continuously in healthy living cells, but then the capacity of repair mechanisms is sufficient to effect cellular integrity. Decay processes become visible, as soon as repair can no more be sufficient. PCD starts as soon as produced energy is permanently insufficient to repress decay. Decreased energy production may arise due to (i) turning off the pivotal tricarbonic acid cycle, (ii) turning off oxidative phosphorylation, (iii) damage of mitochondria, and (iv) inhibition of mitochondrial biogenesis regarding both the mitochondrial and the nuclear part. The consequence of this kind of decreased energy production will be a massive, inefficient fermentative energy production with enormous amounts of lactic acid. Increasing acidity and falling pH will slow down enzymatic activities and thus also intracellular processes. As soon as energy for repair has become insufficient, cellular decay becomes irreversible and the cell will die. Thus, the mitochondrial apoptotic pathway is suggested to arise due to low mitochondrial energy production. For optimal functioning cells need adequate internal conditions and cellular morphology. Cellular morphology depends on (i) the intracellular turgor, (ii) the intracellular cytoskeleton, and (iii) close intercellular contact with neighbour cells. Lack of energy implies decrease of turgor and, consequently, a strong decline of conditions needed for adequate functioning of the cell. Thus, if this lack of energy cannot be repaired in time, it will contribute to cellular decay. Various cellular components or systems that are not directly linked to mitochondria, may be functionally inhibited or damaged and thus contribute to apoptosis. These components or systems that probably constitute the non-mitochondrial pathway are (i) the cellular uptake systems for energy-rich substrates, (ii) extra-mitochondrial enzymes that are involved in non-mitochondrial processes of oxidative energy production, (iii) cytoplasmatic, non-mitochondrial protein synthesis, (iv) the system that regulates osmotic conditions and turgor, and (v) the synthesis and repair of the cytoskeleton. After this careful reflection I am convinced that apoptosis is merely the complex machinery of cellular decay after energy generation has irreversibly stopped. Therefore, apoptosis research for health care should be focussed on processes that hinder energy production. For therapeutic aims research should be focussed on metabolic aspects of energy production and on mitochondrial processes.
authors.forename: Ger P A
authors.initials: GP
authors.lastname: Bongaerts
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002468:Cell Physiological Phenomena; D004734:Energy Metabolism; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000502:physiology; D008938:Mitosis / Q000502:physiology*