TY - JOUR
T1 - VDAC, a multi-functional mitochondrial protein as a pharmacological target
AU - Shoshan-Barmatz, Varda
AU - Ben-Hail, Danya
N1 - Funding Information:
This research was supported by grants from the Israel Science Foundation , the Israel Cancer Association and the Chief Scientist's Office, Ministry of Health, Government of Israel .
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Regulation of mitochondrial physiology requires an efficient exchange of molecules between mitochondria and the cytoplasm via the outer mitochondrial membrane (OMM). The voltage-dependent anion channel (VDAC) lies in the OMM and forms a common pathway for the exchange of metabolites between the mitochondria and the cytosol, thus playing a crucial role in the regulation of metabolic and energetic functions of mitochondria. VDAC is also recognized to function in mitochondria-mediated apoptosis and in apoptosis regulation via interaction with anti-apoptotic proteins, namely members of Bcl-2 family, and the pro-survival protein, hexokinase, overexpressed in many cancer types. Thus, VDAC appears to be a convergence point for a variety of cell survival and cell death signals, mediated by its association with various ligands and proteins. In this article, we review mammalian VDAC, specifically focusing on VDAC1, addressing its functions in cell life and the regulation of apoptosis and its involvement in several diseases. Additionally, we provide insight into the potential of VDAC1 as a rational target for novel therapeutics.
AB - Regulation of mitochondrial physiology requires an efficient exchange of molecules between mitochondria and the cytoplasm via the outer mitochondrial membrane (OMM). The voltage-dependent anion channel (VDAC) lies in the OMM and forms a common pathway for the exchange of metabolites between the mitochondria and the cytosol, thus playing a crucial role in the regulation of metabolic and energetic functions of mitochondria. VDAC is also recognized to function in mitochondria-mediated apoptosis and in apoptosis regulation via interaction with anti-apoptotic proteins, namely members of Bcl-2 family, and the pro-survival protein, hexokinase, overexpressed in many cancer types. Thus, VDAC appears to be a convergence point for a variety of cell survival and cell death signals, mediated by its association with various ligands and proteins. In this article, we review mammalian VDAC, specifically focusing on VDAC1, addressing its functions in cell life and the regulation of apoptosis and its involvement in several diseases. Additionally, we provide insight into the potential of VDAC1 as a rational target for novel therapeutics.
KW - Apoptosis
KW - Cytochrome c
KW - Hexokinase
KW - Mitochondria
KW - Reactive oxygen species
KW - VDAC
UR - http://www.scopus.com/inward/record.url?scp=84856510610&partnerID=8YFLogxK
U2 - 10.1016/j.mito.2011.04.001
DO - 10.1016/j.mito.2011.04.001
M3 - Review article
C2 - 21530686
AN - SCOPUS:84856510610
SN - 1567-7249
VL - 12
SP - 24
EP - 34
JO - Mitochondrion
JF - Mitochondrion
IS - 1
ER -
