Granzymes and Mitochondria

Cytotoxic T lymphocytes and natural killer cells eliminate infected cells from the organism by triggering programmed cell death (apoptosis). The contents of the lytic granules of killer cells, including pore-forming proteins perforins and proteolytic enzymes granzymes, are released with the followin...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2020-02, Vol.85 (2), p.131-139
Main Author: Kiselevsky, D. B.
Format: Article
Language:English
Subjects:
Activation
Analysis
Animals
Apoptosis
BID protein
BIM protein
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Caspase-3
Cell Death
Cytochrome
Cytochrome c
Cytochromes
Cytoplasm
Cytotoxicity
DNA damage
Electron transport chain
Endopeptidases
Endoplasmic reticulum
Granule cells
Granzyme B
Granzymes - metabolism
Humans
Life Sciences
Lymphocytes
Lymphocytes T
Mcl-1 protein
Microbiology
Mitochondria
Mitochondria - metabolism
Mortality
Natural killer cells
Nuclease
p53 Protein
Perforin
Pore formation
Pore-forming proteins
Proteases
Proteins
Proteolysis
Proteolytic enzymes
Reactive oxygen species
Reactive Oxygen Species - metabolism
Review
Translocation
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Description
Summary:Cytotoxic T lymphocytes and natural killer cells eliminate infected cells from the organism by triggering programmed cell death (apoptosis). The contents of the lytic granules of killer cells, including pore-forming proteins perforins and proteolytic enzymes granzymes, are released with the following penetration of the released proteins into the target cells. Granzyme B initiates mitochondria-dependent apoptosis via (i) proapoptotic Bid protein, (ii) Mcl-1 and Bim proteins, or (iii) p53 protein. As a result, cytochrome c is released from the mitochondria into the cytoplasm, causing formation of apoptosomes that initiate the proteolytic cascade of caspase activation. Granzymes M, H, and F cause cell death accompanied by the cytochrome c release from the mitochondria. Granzyme A induces generation of reactive oxygen species (ROS), which promotes translocation of the endoplasmic reticulum-associated SET complex to the nucleus where it is cleaved by granzyme A, leading to the activation of nucleases that catalyze single-strand DNA breaks. Granzymes A and B penetrate into the mitochondria and cleave subunits of the respiratory chain complex I. One of the complex I subunits is also a target for caspase-3. Granzyme-dependent damage to complex I leads to the ROS generation and cell death.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297920020017