VDAC2-specific cellular functions and the underlying structure.
Voltage Dependent Anion-selective Channel 2 (VDAC2) contributes to oxidative metabolism by sharing a role in solute transport across the outer mitochondrial membrane (OMM) with other isoforms of the VDAC family, VDAC1 and VDAC3. Recent studies revealed that VDAC2 also has a distinctive role in mediating sarcoplasmic reticulum to mitochondria local Ca(2+) transport at least in cardiomyocytes, which is unlikely to be explained simply by the expression level of VDAC2. Furthermore, a strictly isoform-dependent VDAC2 function was revealed in the mitochondrial import and OMM-permeabilizing function of pro-apoptotic Bcl-2 family proteins, primarily Bak in many cell types. In addition, emerging evidence indicates a variety of other isoform-specific engagements for VDAC2. Since VDAC isoforms display 75% sequence similarity, the distinctive structure underlying VDAC2-specific functions is an intriguing problem. In this paper we summarize studies of VDAC2 structure and functions, which suggest a fundamental and exclusive role for VDAC2 in health and disease. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
MitoCare Center for Mitochondrial Imaging Research and Diagnostics, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: shamim.naghdi@jefferson.edu.
Shamim
S
Naghdi
MitoCare Center for Mitochondrial Imaging Research and Diagnostics, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: gyorgy.hajnoczky@jefferson.edu.
György
G
Hajnóczky
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D017136:Ion Transport; D008322:Mammals / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013256:Steroids / Q000378:metabolism; D013329:Structure-Activity Relationship; D050996:Voltage-Dependent Anion Channel 2 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D013256:Steroids; D050996:Voltage-Dependent Anion Channel 2
Apoptosis; Bak; Bax; Bid; Calcium; Mitochondria; Sarcoplasmic reticulum; VDAC2