Аннотация:Mitochondria are multifunctional structures involved in a number
of energy-producing and transducing processes and beyond
these. Participation of mitochondria in cell death has received
significant support while recent data point to their role in programmed
organ failure and organismal death. The clearly programmed
syndrome of multiple, simultaneous failure of a
number of organs (MOF) is obviously a particular example and
a source of phenoptotic death of a system. Histological examination
often shows no signs of necrotic or apoptotic cell death in a
failed tissue, however, signs of mitochondrial dysfunction have
been repeatedly described. The mechanisms of mitochondriamediated
phenoptosis may include generation of ROS and damage-
associated molecular patterns (DAMPs) by mitochondria.
DAMPs have been shown to mediate a fatal systemic inflammatory response syndrome caused by trauma through initial activation
of innate immunity. Sepsis, a possible cause of MOF, was
observed as the intermediate stage between the initial damage
and MOF. However, in the syndrome of systemic inflammatory
response observed in trauma or hemorrhagic shock the blood is
sterile. The clinical picture of this phenomenon is not distinguishable
from that of bacterial sepsis and mortality is very high in
both cases. A unique role in a deadly cascade resulting in organism
failure belongs to the kidney. It has been known that any
pathology accompanied by acute renal failure increases mortality
by 15–60%. In our experiments with rats when one of the two
kidneys is removed and the remaining kidney is exposed to ischemia/
reperfusion, acute renal failure develops. However, in rats
pre-treated with the mitochondria-targeted antioxidant SkQR1
the severity of renal failure is significantly reduced. In addition,
the other mitochondrial antioxidant, SkQ1, did not improve
renal function although both antioxidants almost completely
abolished animal death which was as high as 70% in the absence
of the antioxidants. We conclude that contrary to popular belief
it was not renal failure that was the cause of animal death but
some control system which is the target of used antioxidants. We
speculate that it is the immune system involved in mitochondrial
signaling that may be responsible for organismal death.