Mitoptosis

Two main forms of mitoptosis are distinguished: 1) associated with a violation of the external and / or 2) internal mitochondrial membranes. In the first case, the mitochondria first condenses, after which its matrix swells and the cristae are fragmented. Finally, the outer membrane is torn and the remnants of the cristal vesicles exit into the cytoplasm. As a rule, mitochondria have a bean-like shape, and when swollen, they take a spherical shape. In the process of mitoptosis due to changes in the inner membrane, the following occurs: the outer mebrana remains unchanged, while a change in cristae is observed. The inner membrane begins to coalesce (condense), followed by liquefaction (loss of density) of the matrix, which leads to degradation of cristae. In cells, a third - mixed - type of mitoptosis is also secreted. Mitochondria condenses, swells, vesicular fragmentation of cristae occurs, as in the first mechanism, but there is no rupture of the outer membrane and mitochondria is absorbed by the autophagosome. ^{[3] [4]}

Mitochondria have their own systems of protection against ROS (enzymes, low molecular weight substances), however, if the concentration of ROS continues to increase, then the cell takes more radical methods of struggle - it causes mitoptosis. Exposure to ROS leads to the conversion of the ATP / ADP antiporter or other anion transporters into non-specific channels capable of transmitting any low molecular weight substances. ATP / ADP antiporter is a mitochondrial inner membrane protein that transports adenine nucleotides. ROS oxidize the SH groups of cysteines facing the matrix. Such channels are called “permeability transition pore-PTP”: “a pore causing a transition (mitochondrial membranes) to a state of high permeability”. The osmotic balance between the matrix and the intermembrane space of mitochondria is violated, ΔΨ (transmembrane electric potential difference) completely disappears. Water rushes into the matrix, diluting the concentrated protein solution (there are much more proteins in the matrix than in the intermembrane space). As a result, the matrix swells, folds of the inner membrane are straightened, and the outer membrane ruptures, the area of ​​which is smaller. In this case, all proteins dissolved in the intermembrane space, and among them cytochrome c , splash into the cytosol. Vnemitochondrial cytochrome c triggers additional reactions to combat ROS. If these defense mechanisms do not work, the mitochondria is forced to self-destruct, since it cannot exist for a long time with open pores. In addition to the release of cytochrome c, the cofactors NAD +, NADP + necessary for mitochondria work out. The important reparative process, which should take place due to the precursor proteins normally transported inside the mitochondria, stops. Thus, a dangerous organelle enters mitoptosis to protect the cell from further risk. ^[2]

Another pathway detrimental to organelles associated with the accumulation of ROS is inactivation of aconitase. Aconitase is an enzyme that performs a reversible reaction of isomerization of citrate and isocitrate , an element of the Krebs cycle . In eukaryotes, 2 isoforms of aconitases are known, one of which is localized in the mitochondrial matrix, the other in the cytoplasm. ^[5] Mitochondrial aconitase is normally associated with mtDNA and it is assumed that it thus performs the function of histones. Inactivation reduces the interaction of aconitase with mtDNA, and as a result, unprotected DNA becomes an affordable target for the harmful effects of oxygen radicals and other destructive effects.