Mitochondrial Membrane Cholesterol, the Voltage Dependent Anion Channel (VDAC), and the Warburg Effect

Overview

Journal J Bioenerg Biomembr

Publisher Springer

Specialties Biochemistry
Biology
Endocrinology

Date 2008 Aug 5

PMID 18677555

Citations 23

Authors

Andrew M Campbell

Samuel H P Chan

Affiliations

Soon will be listed here.

Abstract

Normal cells of aerobic organisms synthesize the energy they require in the form of ATP via the process of oxidative phosphorylation. This complex system resides in the mitochondria of cells and utilizes oxygen to produce a majority of cellular ATP. However, in most tumors, especially those with elevated cholesterogenesis, there is an increased reliance on glycolysis for energy, even in conditions where oxygen is available. This aerobic glycolysis (the Warburg effect) has far reaching ramifications on the tumor itself and the cells that surround it. In this brief review, we will discuss how abnormally high membrane cholesterol levels can result in a subsequent deficiency of oxidative energy production in mitochondria from cultured Morris hepatoma cells (MH-7777). We have identified the voltage dependent anion channel (VDAC) as a necessary component of a protein complex involved in mitochondrial membrane cholesterol distribution and transport. Work in our laboratory demonstrates that the ability of VDAC to influence mitochondrial membrane cholesterol distribution may have implications on mitochondrial characteristics such as oxidative phosphorylation and induction of apoptosis, as well as the propensity of cancer cells to exhibit a glycolytic phenotype.

Citing Articles

Mitochondrial Proteomes in Neural Cells: A Systematic Review.

Nusir A, Sinclair P, Kabbani N Biomolecules. 2023; 13(11).

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E as in Enigma: The Mysterious Role of the Voltage-Dependent Anion Channel Glutamate E73.

Rister A, Gudermann T, Schredelseker J Int J Mol Sci. 2023; 24(1).

PMID: 36613710 PMC: 9820230. DOI: 10.3390/ijms24010269.

Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets.

He J, Siu M, Ngan H, Chan K Front Oncol. 2021; 11:738177.

PMID: 34820325 PMC: 8606538. DOI: 10.3389/fonc.2021.738177.

Cell-free electrophysiology of human VDACs incorporated into nanodiscs: An improved method.

Conti Nibali S, Di Rosa M, Rauh O, Thiel G, Reina S, De Pinto V Biophys Rep (N Y). 2021; 1(1):None.

PMID: 34568862 PMC: 8448298. DOI: 10.1016/j.bpr.2021.100002.

Warburg's Ghost-Cancer's Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis.

Coleman P, Parlo R Front Cell Dev Biol. 2021; 9:626316.

PMID: 33777935 PMC: 7994618. DOI: 10.3389/fcell.2021.626316.

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