Abstract
This is a response to a letter by Thinnes (1) We are aware of a long-standing controversy and ongoing debate regarding localization of the voltage-dependent anion channel (VDAC) to the mitochondrial outer membrane (VDAC) and the plasmalemmal membrane (pl-VDAC), as well as the existence of the maxi-anion channel in the plasma membrane, and wish to address some misinterpretations of our findings by Dr. Thinnes. Contrary to Dr. Thinnes' contention that these proteins are all derived from the same gene, we have strong reservations regarding this conclusion and consider it an unresolved question. Dr. Rostovtseva, a corresponding author for this article, addressed this issue and questioned the validity of pl-VDAC identification in the plasma membrane using solely a commercially available monoclonal antibody that was raised against a 19-amino acid portion of the N terminus of human VDAC1 (2). Others have shown that the antibody that Dr. Thinnes claims is specific for VDAC exhibits nonspecific binding. For instance, Yu and Forte (3, 4) concluded “if VDAC molecules are present at nonmitochondrial locations in mammalian cells, these are unlikely to be the known products of the HVDAC1 or HVDAC2 genes.” Others have shown that this antibody labels the plasma membrane regardless of the fact that VDAC genes were knocked out (5). Most recently, a detailed analysis of the “pros and cons” of VDAC localization in the plasma membrane and its confusion with the maxi-anion channel has been presented by Sabirov and Merzlyak in their latest review (6). These authors concluded that “the hypothesis of plasmalemmal VDAC as the maxi-anion channel did not withstand the test by genetic manipulation of VDAC expression.” In conclusion, our study was focused entirely on the properties of VDAC from the mitochondrial outer membrane; therefore, discussion of possible VDAC N-terminal exposure on the plasma membrane surface is totally irrelevant to this work. Our experiments did not aim to test the position of the VDAC1 N terminus in the channel's closed conformation. We cannot rule out the possibility that, when closed, the first amino acids of the VDAC N terminus could be exposed at the channel entrance, but these speculations are beyond our present study.
Highlights
We are aware of a long-standing controversy and ongoing debate regarding localization of the voltage-dependent anion channel (VDAC) to the mitochondrial outer membrane (VDAC) and the plasmalemmal membrane, as well as the existence of the maxi-anion channel in the plasma membrane, and wish to address some misinterpretations of our findings by Dr Thinnes
Dr Rostovtseva, a corresponding author for this article, addressed this issue and questioned the validity of pl-VDAC identification in the plasma membrane using solely a commercially available monoclonal antibody that was raised against a 19-amino acid portion of the N terminus of human VDAC1 [2]
Yu and Forte [3, 4] concluded “if VDAC molecules are present at nonmitochondrial locations in mammalian cells, these are unlikely to be the known products of the HVDAC1 or HVDAC2 genes.”
Summary
Published in the U.S.A. Reply to Thinnes: To Include Plasmalemmal VDAC/Porin Pays This is a response to a letter by Thinnes [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
