Bioenergetic aspects of apoptosis, necrosis and mitoptosis

Abstract

In this review I summarize interrelations between bioenergetic processes and such programmed death phenomena as cell suicide (apoptosis and necrosis) and mitochondrial suicide (mitoptosis). The following conclusions are made. (I) ATP and rather often mitochondrial hyperpolarization (i.e. an increase in membrane potential, delta psi) are required for certain steps of apoptosis and necrosis. (II) Apoptosis, even if it is accompanied by delta psi and [ATP] increases at its early stage, finally results in a delta psi collapse and ATP decrease. (III) Moderate (about three-fold) lowering of [ATP] for short and long periods of time induces apoptosis and necrosis, respectively. In some types of apoptosis and necrosis, the cell death is mediated by a delta psi-dependent overproduction of ROS by the initial (Complex I) and the middle (Complex III) spans of the respiratory chain. ROS initiate mitoptosis which is postulated to rid the intracellular population of mitochondria from those that are ROS overproducing. Massive mitoptosis can result in cell death due to release to cytosol of the cell death proteins normally hidden in the mitochondrial intermembrane space.

Mitochondrion-mediated apoptosis induced by Rana grylio virus infection in fish cells

“…Changes in Dwm are considered as an important event in the effect phase of apoptosis induced by many apoptotic stimuli, including virus infection [31]. Even if it is accompanied by Dwm increases at its early stage, apoptosis finally results in a Dwm collapse [32]. In the RGV-infected FHM cells, the Dwm collapse also appears similar changes.…”

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

“…Notably, cytotoxic agents are shown to induce necrotic cell death in apoptosis-defective cancer cells, 93 probably because necroptosis is principally induced when a cell cannot die via apoptotic pathways. 94 On the other hand, conventional therapy-resistant cancer stem cells (CSCs) have a higher antiapoptotic activity than that of their counterparts. 95,96 Therefore, it would be vital to clarify the key machinery of not only the necroptosis induction in cancer cells for CSC-directed therapeutic application but also the resultant immunogenicity to modulate antitumor immunity.…”

Autophagy, Apoptosis, Mitoptosis and Necrosis: Interdependence Between Those Pathways and Effects on Cancer

“…Necrosis has long been considered an accidental and uncontrolled, non-programmed form of cell death whereby dramatic changes in crucial cell parameters of metabolism and cell structure take place (Skulachev 2006). The accidental necrosis is in general caused by chemical or physical injury (Vandenabeele et al 2010).…”

“…This is particularly frequent when a cell for one or other reason (i.e. low ATP-level) is unable to die by apoptosis (Los et al 2002;Skulachev 2006). Necrosis is typically not associated with activation of caspases (it rather may be a result of their inhibition) (Los et al 2002); it is characterized by swelling of the endoplasmic reticulum, mitochondria, and cytoplasm, with subsequent rupture of the plasma membrane and lysis of the cells (Schweichel and Merker 1973).…”