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Comment
. 2018 Nov 19;9(12):1151.
doi: 10.1038/s41419-018-1206-5.

BAP1 regulates different mechanisms of cell death

El Bachir Affar  1 , Michele Carbone  2
Affiliations
Comment

BAP1 regulates different mechanisms of cell death

El Bachir Affar et al. Cell Death Dis. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

None. For full disclosure Dr. Carbone declares that he has pending patent applications on BAP1, a patent using anti-HMGB1 monoclonal antibody or other HMGB1 antibodies as a novel mesothelioma therapeutic strategy, Patent No.: 9,561,274 issued, and a patent HMGB1 as a biomarker for asbestos exposure and mesothelioma early detection Application No.: 14/123,722 Patent No.: 9,244,074. Dr. Carbone is a board certified Pathologist and provides consultation for mesothelioma expertise and diagnosis, including paid medical-legal consulting. E.B.A. has nothing to disclose.

Figures

Fig. 1
Fig. 1. Roles of the deubiquitylase and tumor suppressor BAP1 in cell death.
The tumor suppressor BAP1 promotes ferroptosis by repressing the expression of SLC7A11, a cystine/glutamate antiporter responsible for the cellular entry of cysteine, a metabolite used for the novo synthesis of reduced glutathione. Inhibition of SLC7A11 expression leads to low levels of reduced glutathione, diminished antioxidant capacity of the cells, thus resulting in Lipid-ROS accumulation and ferroptosis. BAP1 deubiquitylates and stabilizes the IP3R3 channel-receptor, thus promoting the release of Ca2+ from the endoplasmic reticulum (ER) into the cytoplasm and mitochondria (Mitoc). High levels of mitochondrial Ca2+, promote cytochrome c release from the mitochondria into the cytoplasm, a process that leads to apoptosis. Therefore, low levels of BAP1 inhibit both apoptosis and ferroptosis, facilitating the survival of DNA damage cells. BAP1 can also inhibit apoptosis by repressing the expression of key ER stress transcription factors with pro-apoptotic functions. The ability of BAP1 to modulate apoptosis and ferroptosis contributes to its tumor suppressor function in vivo. GSL: glutamate-cysteine ligase; GSH: Reduced glutathione; GSSG: oxidized glutathione; GR: Glutathione Reductase; GPX4: Glutathione Peroxidase 4; VDAC: Voltage-dependent anion channel; MCU: mitochondrial Ca2+ uniporter; Ub: Ubiquitin
See this image and copyright information in PMC

Comment on

  • BAP1 links metabolic regulation of ferroptosis to tumour suppression.
    Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P, Sirohi K, Li X, Wei Y, Lee H, Zhuang L, Chen G, Xiao ZD, Hung MC, Chen J, Huang P, Li W, Gan B. Zhang Y, et al. Nat Cell Biol. 2018 Oct;20(10):1181-1192. doi: 10.1038/s41556-018-0178-0. Epub 2018 Sep 10. Nat Cell Biol. 2018. PMID: 30202049 Free PMC article.

References

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