Mitochondrial Entry of Cytotoxic Proteases: A New Insight into the Granzyme B Cell Death Pathway
Author
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-21
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
The mitochondria represent an integration and amplification hub for various death pathways including that mediated by granzyme B (GB), a granule enzyme expressed by cytotoxic lymphocytes.
GB activates the proapoptotic B cell CLL/lymphoma 2 (Bcl-2) family member BH3-interacting domain death agonist (BID) to switch on the intrinsic mitochondrial death pathway, leading to Bcl-2-associated X protein (Bax)/Bcl-2 homologous antagonist/killer- (Bak-) dependent mitochondrial outer membrane permeabilization (MOMP), the dissipation of mitochondrial transmembrane potential (ΔΨm), and the production of reactive oxygen species (ROS).
GB can also induce mitochondrial damage in the absence of BID, Bax, and Bak, critical for MOMP, indicating that GB targets the mitochondria in other ways.
Interestingly, granzyme A (GA), GB, and caspase 3 can all directly target the mitochondrial respiratory chain complex I for ROS-dependent cell death.
Studies of ROS biogenesis have revealed that GB must enter the mitochondria for ROS production, making the mitochondrial entry of cytotoxic proteases (MECP) an unexpected critical step in the granzyme death pathway.
MECP requires an intact ΔΨm and is mediated though Sam50 and Tim22 channels in a mtHSP70-dependent manner.
Preventing MECP severely compromises GB cytotoxicity.
In this review, we provide a brief overview of the canonical mitochondrial death pathway in order to put into perspective this new insight into the GB action on the mitochondria to trigger ROS-dependent cell death.
American Psychological Association (APA)
Martinvalet, Denis. 2019. Mitochondrial Entry of Cytotoxic Proteases: A New Insight into the Granzyme B Cell Death Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1206167
Modern Language Association (MLA)
Martinvalet, Denis. Mitochondrial Entry of Cytotoxic Proteases: A New Insight into the Granzyme B Cell Death Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1206167
American Medical Association (AMA)
Martinvalet, Denis. Mitochondrial Entry of Cytotoxic Proteases: A New Insight into the Granzyme B Cell Death Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1206167
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206167