LETTER TO THE EDITOR
On GxxxG in N-terminal stretches of type-1 VDAC/porin: critical
in vertebrate apoptosis, missing in plants
Friedrich P. Thinnes
Received: 14 February 2012 / Accepted: 29 February 2012 / Published online: 27 March 2012
Ó Springer Science+Business Media B.V. 2012
The recently published paper by Teijido et al. 2012 refines
the voltage-dependent anion channel (VDAC) model pro-
posed by Marco Colombini (Colombini 2009). It also refers
to data on the accessibility of the VDAC’s N-terminus at
the cytosolic side of mitochondria (De Pinto et al. 1991;
Guo et al. 1995). The traditional view is in trouble since
crystallographic investigations on mammalian type-1
VDAC point to a ß-barrel structure, with the N-terminal
comprising a partially helical stretch of about 25 amino
acids resting inside the lumen (Hiller et al. 2008; Colom-
bini 2009; Thinnes 2009a).
In terms of the plasmalemmal type-1 VDAC in verte-
brates, the regulatory volume decrease (RVD) that occurs
in hypotonically stimulated HeLa cells can be blocked
by pre-incubation with antibodies which recognize epi-
tope(s) inside the acetylated N-terminal stretch, including
Ac-Ala to AA12 of human type-1 VDAC, while cell
swelling remains unaffected (Thinnes et al. 2000; for video
monitoring, see http://www.futhin.de). The volume-sensi-
tive organic osmolyte anion channel (VSOAC), which is a
‘‘maxi-anion’’ channel and unknown in molecular terms,
is critical in RVD as it allows the exit of chloride and
other anions/osmolytes (ATP, amino acids, taurine) from
cells.
Plasmalemmal type-1 VDAC is a candidate for the
VSOAC (Thinnes et al. 1990, 2000; Okada et al. 2004;
Parsons et al. 2011). Additionally, this VDAC is engaged
in the apoptotic processes that occur in vertebrates, starting
with apoptotic volume decrease (AVD) (Elinder et al.
2005; Akanda et al. 2008; Thinnes 2009b, c; Thinnes 2011;
Hur et al. 2012; Marin et al. 2012). For a recent discussion
of data on cell membrane standing VDAC, the reader is
referred to Sabirov and Merzlyak (2011). However,
blocking experiments on the RVD or AVD of mammalian
cells indicate that whenever VDAC closes its N-terminal
end moves out of its lumen towards the cell surface. When
the VDAC reopens, the pore collapses around the N-ter-
minal part inside the channel lumen.
Increasing attention is focusingon a pentapeptideinside the
N-terminal stretch of type-1 VDAC. Vertebrate type-1 VDAC
channels carry the sequences GygfG/GyafG (Reymann et al.
1999) in positions 20ff of their N-terminal stretches, which
are proximally connected to ß-sheet-1 and cross the lumen
towards the cytosol or the cell surface, respectively. Interest-
ingly, this pentapeptide functions as an ATP-binding site of
vertebrate type-1 VDAC (Flo
¨
rke et al. 1994;Yehezkeletal.
2007), and GxxxG is also well established as an aggregation/
membrane perturbation motif (Curran and Engelman 2003;
Munter et al. 2010).
In contrast to vertebrate type-1 VDAC plant VDAC
isoforms do not show corresponding GxxxG motifs in their
N-terminal stretches (see following section). Nevertheless,
plant cells express VDAC in mitochondria as well as in
their plasmalemma (Robert et al. 2012; Tateda et al. 2012;
Homble
´
et al.
2011).
From here questions arise: (1) on differences concerning
VDAC closure in cell membranes of vertebrates and plants;
(2) does the lack of a GxxxG motif near the N-terminus of
plant VDAC point to intrinsic processes as the only
This paper is a synopsis of two recent papers dealing with the multi-
compartment expression pattern and function of plant voltage-
dependent anion channels (VDACs) (Robert et al. 2012) and the
three-dimensional structure of the mammalian type-1 VDAC (Teijido
et al. 2012), respectively. These papers have raised a number of
questions for discussion.
F. P. Thinnes (&)
Baumschulenweg 5, 37083 Go
¨
ttingen, Germany
e-mail: futhin@t-online.de
123
Plant Mol Biol (2012) 79:1–3
DOI 10.1007/s11103-012-9900-7
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