VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges

Most anionic metabolites including respiratory substrates, glycolytic adenosine triphosphate (ATP), and small cations that enter mitochondria, and mitochondrial ATP moving to the cytosol, cross the outer mitochondrial membrane (OMM) through voltage dependent anion channels (VDAC). The closed states...

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Autores principales: Heslop, Kareem A., Milesi, María Verónica, Maldonado, Eduardo N.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Ciencias Médicas
Cancer
Glycolysis
Metabolic flexibility
Metabolic reprogramming
Metabolism
Mitochondria
Voltage dependent anion channels
Warburg
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/130014
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-130014
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Cancer
Glycolysis
Metabolic flexibility
Metabolic reprogramming
Metabolism
Mitochondria
Voltage dependent anion channels
Warburg
spellingShingle Ciencias Médicas
Cancer
Glycolysis
Metabolic flexibility
Metabolic reprogramming
Metabolism
Mitochondria
Voltage dependent anion channels
Warburg
Heslop, Kareem A.
Milesi, María Verónica
Maldonado, Eduardo N.
VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
topic_facet Ciencias Médicas
Cancer
Glycolysis
Metabolic flexibility
Metabolic reprogramming
Metabolism
Mitochondria
Voltage dependent anion channels
Warburg
description Most anionic metabolites including respiratory substrates, glycolytic adenosine triphosphate (ATP), and small cations that enter mitochondria, and mitochondrial ATP moving to the cytosol, cross the outer mitochondrial membrane (OMM) through voltage dependent anion channels (VDAC). The closed states of VDAC block the passage of anionic metabolites, and increase the flux of small cations, including calcium. Consequently, physiological or pharmacological regulation of VDAC opening, by conditioning the magnitude of both anion and cation fluxes, is a major contributor to mitochondrial metabolism. Tumor cells display a pro-proliferative Warburg phenotype characterized by enhanced aerobic glycolysis in the presence of partial suppression of mitochondrial metabolism. The heterogeneous and flexible metabolic traits of most human tumors render cells able to adapt to the constantly changing energetic and biosynthetic demands by switching between predominantly glycolytic or oxidative phenotypes. Here, we describe the biological consequences of changes in the conformational state of VDAC for cancer metabolism, the mechanisms by which VDAC-openers promote cancer cell death, and the advantages of VDAC opening as a valuable pharmacological target. Particular emphasis is given to the endogenous regulation of VDAC by free tubulin and the effects of VDAC-tubulin antagonists in cancer cells. Because of its function and location, VDAC operates as a switch to turn-off mitochondrial metabolism (closed state) and increase aerobic glycolysis (pro-Warburg), or to turn-on mitochondrial metabolism (open state) and decrease glycolysis (anti-Warburg). A better understanding of the role of VDAC regulation in tumor progression is relevant both for cancer biology and for developing novel cancer chemotherapies.
format Articulo
Articulo
author Heslop, Kareem A.
Milesi, María Verónica
Maldonado, Eduardo N.
author_facet Heslop, Kareem A.
Milesi, María Verónica
Maldonado, Eduardo N.
author_sort Heslop, Kareem A.
title VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
title_short VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
title_full VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
title_fullStr VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
title_full_unstemmed VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
title_sort vdac modulation of cancer metabolism: advances and therapeutic challenges
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/130014
work_keys_str_mv AT heslopkareema vdacmodulationofcancermetabolismadvancesandtherapeuticchallenges
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AT maldonadoeduardon vdacmodulationofcancermetabolismadvancesandtherapeuticchallenges
bdutipo_str Repositorios
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