In:
EMBO Molecular Medicine, EMBO, Vol. 6, No. 5 ( 2014-05), p. 624-639
Abstract:
image Weak mitochondrial uncouplers prevent neoangiogenesis in vitro and in vivo by depleting cellular energy reserves in proliferating but not normal quiescent endothelial cells (ECs). New vessel formation during tumor growth requires EC proliferation and increased oxidative phosphorylation to meet the greater energy demand during angiogenesis. Weak mitochondrial uncouplers prevent neoangiogenesis by depleting cellular energy reserves in proliferating but not normal quiescent ECs. Proliferating ECs are sensitized to mitochondrial uncouplers by a reduction in membrane potential and lower respiratory reserve capacity. Genetic accumulation of mitochondrial DNA mutations in mitochondrial mutator mice highlights the link between reduced OxPhos activity and impaired angiogenic response. Weak mitochondrial uncouplers could be clinically valuable in controlling pathological neoangiogenesis while sparing normal vasculature and complementing cytostatic drugs in cancer treatment.
Type of Medium:
Online Resource
ISSN:
1757-4676
,
1757-4684
DOI:
10.1002/emmm.201303016
Language:
English
Publisher:
EMBO
Publication Date:
2014
detail.hit.zdb_id:
2485479-7
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