Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation

Cancer & Metabolism
M Christiane Brahimi-HornN M Mazure

Abstract

Mitochondria are more than just the powerhouse of cells; they dictate if a cell dies or survives. Mitochondria are dynamic organelles that constantly undergo fusion and fission in response to environmental conditions. We showed previously that mitochondria of cells in a low oxygen environment (hypoxia) hyperfuse to form enlarged or highly interconnected networks with enhanced metabolic efficacy and resistance to apoptosis. Modifications to the appearance and metabolic capacity of mitochondria have been reported in cancer. However, the precise mechanisms regulating mitochondrial dynamics and metabolism in cancer are unknown. Since hypoxia plays a role in the generation of these abnormal mitochondria, we questioned if it modulates mitochondrial function. The mitochondrial outer-membrane voltage-dependent anion channel 1 (VDAC1) is at center stage in regulating metabolism and apoptosis. We demonstrated previously that VDAC1 was post-translationally C-terminal cleaved not only in various hypoxic cancer cells but also in tumor tissues of patients with lung adenocarcinomas. Cells with enlarged mitochondria and cleaved VDAC1 were also more resistant to chemotherapy-stimulated cell death than normoxic cancer cells. Transcriptome analys...Continue Reading

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Citations

Apr 16, 2016·Biochimica Et Biophysica Acta·Tasleem ArifVarda Shoshan-Barmatz
Sep 15, 2016·Frontiers in Oncology·N M Mazure
Apr 15, 2017·Journal of Applied Physiology·Raphael R Fagundes, Cormac T Taylor
May 1, 2020·Metallomics : Integrated Biometal Science·M OmidiB J C Luthringer-Feyerabend
Aug 9, 2020·Cancer Management and Research·Huining TianGuixia Wang
Dec 20, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Pandian NagakannanEftekhar Eftekharpour
Aug 19, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Francesca GuarinoAngela Messina
Jul 25, 2021·Cancers·Julien AncelValérian Dormoy

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Datasets Mentioned

BETA
GSE63247

Methods Mentioned

BETA
fluorescence-activated cell sorter
transfect
flow cytometry
Assay

Software Mentioned

Ingenuity Pathway Analysis TM ( IPA TM )
SPSS
Excel
Ingenuity Pathway Analysis
IPA
Limma

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