Mitochondrial voltage-dependent anion-selective channel (VDAC): a global player in cells.
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Date
2016-06, 2017-08
Authors
Shuvo, Sabbir
Journal Title
Journal ISSN
Volume Title
Publisher
NRC research press
Elsevier
Elsevier
Abstract
Mitochondria are primary ATP producing organelles and are involved in many cellular signalling pathways. Mitochondrial porin, which forms voltage-dependent anion-selective channels (VDAC) in the mitochondrial outer membrane (MOM), can be folded into a 19 β-stranded barrel. The N-terminus of the protein is external to the barrel, and contains α-helical structure. VDAC play roles in the transport of metabolites across the MOM and influences mitochondrial bioenergetics.
Here, Neurospora crassa VDAC was used as a model to investigate the effects of a partial deletion of the N-terminal segment. The protein, ΔN2-12porin, is assembled into the outer membrane, albeit at lower levels than the wild-type (WT) protein. The resulting strain displays electron transport chain deficiencies, concomitant expression of alternative oxidase, and decreased growth rates. Most of the genes that are expressed in high levels in porin-less N. crassa are expressed at levels like WT or are slightly increased in ΔN2-12porin strain. Thus, although the N-terminal segment of VDAC is required for complete function in vivo, low levels of a protein lacking part of the N-terminus can rescue some of the defects associated with the absence of porin.
In the second study, in comparison with WT, the VDAC-less mitochondria display lower complex I and respiratory control ratio, but higher ROS production capacity under non-phosphorylating conditions. Membrane depolarization by subsequent addition of ADP was significantly lower than that observed in wild-type organelles. Mitochondria harbouring about 50% of the wild-type amount of VDAC have elevated complex II activity and ROS production capacity compared to wild-type. Similarly, in mitochondria expressing low levels of an N-terminally truncated VDAC (ΔN2-12porin), higher ROS production capacity was detected compared to wild-type.
Lastly, proteomic analyses of cytosolic proteins in a VDAC-less N. crassa and Saccharomyces cerevisiae strains revealed proteins related to protein synthesis are less abundant; this includes those involved in amino acid and nucleotide metabolism. In contrast, proteins involved in aerobic respiration, in the TCA cycle, carbohydrate and sugar metabolism and oxidative stress responses were more abundant. Additionally, the absence of VDAC influences the composition of mitochondrial membrane, unfolded protein response and target of rapamycin pathways.
Overall these studies revealed the functions associated with the N-terminal of VDAC and the global roles of VDAC.
Description
Keywords
VDAC, Mitochondria, Bioenergetics, ROS, Neurospora
Citation
S.R. Shuvo, U. Kovaltchouk, A. Zubaer, A. Kumar, W.A.T. Summers, L.J. Donald, G. Hausner, D.A. Court, Functional characterization of an N-terminally-truncated mitochondrial porin expressed in Neurospora crassa, Can. J. Microbiol. 68 (2017) 730–738. doi:10.1139/cjm-2016-0764.
S.R. Shuvo, F.G. Ferens, D.A. Court, The N-terminus of VDAC: structure, mutational analysis, and a potential role in regulating barrel shape, Biochim. Biophys. Acta - Biomembr. 1858 (2016) 1350–1361. doi:10.1016/j.bbamem.2016.03.017.
S.R. Shuvo, F.G. Ferens, D.A. Court, The N-terminus of VDAC: structure, mutational analysis, and a potential role in regulating barrel shape, Biochim. Biophys. Acta - Biomembr. 1858 (2016) 1350–1361. doi:10.1016/j.bbamem.2016.03.017.