The regulated cell death apoptosis enables redundant or compromised cells in ontogeny
and homeostasis to remove themselves receptor-dependent after extrinsic signaling or after internal
stress by BCL-2 proteins on the outer mitochondrial membrane (OMM). Mitochondrial BCL-2 proteins
are also often needed for receptor-mediated signaling in apoptosis. Then, the truncated BH3-only
protein BID (tBID) blocks retrotranslocation of the pro-apoptotic BCL-2 proteins BAX and BAK from
the mitochondria into the cytosol. BAX and BAK in turn permeabilize the OMM. Although the BCL-2
proteins are controlled by a complex regulatory network, a specific mechanism for the inhibition
of tBID remained unknown. Curiously, it was suggested that hexokinases, which channel glucose
into the metabolism, have an intriguing function in the regulation of apoptosis. Recent analysis of
transient hexokinase interactions with BAX revealed its participation in the inhibition of BAX and
also BAK by retrotranslocation from mitochondria to the cytosol. In contrast to general apoptosis
inhibition by anti-apoptotic BCL-2 proteins, hexokinase I and hexokinase 2 specifically inhibit tBID
and thus the mitochondrial apoptosis pathway in response to death receptor signaling. Mitochondrial
hexokinase localization and BH3 binding of cytosolic hexokinase domains are prerequisites for
protection against receptor-mediated cell death, whereas glucose metabolism is not. This mechanism
protects cells from apoptosis induced by cytotoxic T cells.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86002 |
| Date | 13 June 2023 |
| Creators | Schöninger, Axel, Wolf, Philipp, Edlich, Frank |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 412 |
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