Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.3 (
complex I
)
8,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth of new tumors, and at the same time, evade ionizing radiation (IR) and chemotherapy. However, the drivers of BTSC resistance to therapy remain unknown. The cytokine receptor for oncostatin M (
OSMR
) regulates BTSC proliferation and glioblastoma tumorigenesis. Here, we report our discovery of a mitochondrial
OSMR
that confers resistance to IR via regulation of oxidative phosphorylation, independent of its role in cell proliferation. Mechanistically,
OSMR
is targeted to the mitochondrial matrix via the presequence translocase-associated motor complex components, mtHSP70 and TIM44.
OSMR
interacts with NADH ubiquinone oxidoreductase 1/2 (NDUFS1/2) of
complex I
and promotes mitochondrial respiration. Deletion of
OSMR
impairs spare respiratory capacity, increases reactive oxygen species, and sensitizes BTSCs to IR-induced cell death. Importantly, suppression of
OSMR
improves glioblastoma response to IR and prolongs lifespan.
...
PMID:OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation. 3280 93
