3.1.1 High Level of Monovalent Cation/Proton Antiporters
Alkaliphiles tend to keep their cytoplasmic pH close to neutral range. To do this
alkaliphilic cells maintain relatively high concentration of H
+ in their cytoplasm.
One way of achieving this is by translocating H
+ from the extracellular environment
into the cell and tightly controlling it. But there are two challenges to do this: the
scarcity of H
+ in the extracellular environment and that the translocation and control
are against concentration gradient. Alkaliphiles evolved mechanisms that solve these
challenges. The monovalent cation/proton antiporters which exchange the intracellular cations such as Na
+ and Li
+ for the extracellular H
+ are believed to be the most
important mechanism that alkaliphiles depend on for intracellular pH homeostasis
[21, 52–59]. Based on the Transporter Classification Database (TCDB; http://www.
tcdb.org), these antiporters are diverse and belong to two superfamilies. The cation/
proton antiporters (CPA) superfamily which consists of five families including
family CPA1 and CPA2 and the Na
+ transporting Mrp superfamily that comprises
three families including family CPA3 which is among the most vital H
+ translocating
antiporters of alkaliphiles [22, 60]. In addition to the families that belong to the
two superfamilies, the Nha families, NhaA, NhaB, NhaC, and NhaD [61] are also
involved in the homeostasis process [62].
Among the monovalent cation/proton antiporters, Na
+
/H
+ antiporters which
exchange cytoplasmic Na
+ for extracellular H
+ seem to be very crucial for pH
homeostasis in alkaliphiles [21, 22, 54, 55]. Moreover, these antiporters are also
used for Na
+ and volume homeostasis as well, like what it does in eukaryotic cells
and their organelles [58, 63–66]. These antiporters avoid the accumulation of Na
+ to
toxic level, while it maintains relatively higher H
+ concentration in the cytoplasm
[21, 67]. The Na
+
/H
+ antiporters are secondary active transporters which use the
transmembrane electrical potential (Δψ) generated by primary ion pumps such as
the respiratory complexes [27] to efflux intracellular Na
+ [21, 54, 55, 68, 69]. In
alkaliphiles, the monovalent cation/proton antiporter-mediated pH homeostasis is
primarily specific for Na
+ but also accommodates Li
+ efflux. On the other hand,
unlike alkaliphiles, neutralophiles use not only Na
+
(Li
+ )/H
+ antiporters but also K
+
/
H
+ antiporters [21, 22]. The specificity of the alkaliphiles monovalent cation/proton
antiporters system to Na
+ is believed to avoid severe depletion of cytoplasmic K
+
that can potentially compromise some cytoplasmic processes [21] and enhances the
cytotoxicity of Na
+ [21, 70, 71]. The other possibility might be that most of the
studied alkaliphiles are adapted to habitats such as soda lakes with high level of Na
+
;
hence, it is ideal for such organisms to evolve a system that relies on the ample
resource (Na
+ ).
Comparative analysis of genes encoding CPAs in genomes of alkaliphiles and
neutralophiles revealed that there is no significant difference in the number of the
genes between alkaliphiles and neutralophiles [54, 55]. However, the aggregate level
of the Na
+
/H
+ antiporter is much higher in alkaliphiles than in neutralophiles [21, 52,
53, 72]. This may be due to the greater burden of pH homeostasis at higher
94
G. Mamo
Alkaliphiles tend to keep their cytoplasmic pH close to neutral range. To do this
alkaliphilic cells maintain relatively high concentration of H
+ in their cytoplasm.
One way of achieving this is by translocating H
+ from the extracellular environment
into the cell and tightly controlling it. But there are two challenges to do this: the
scarcity of H
+ in the extracellular environment and that the translocation and control
are against concentration gradient. Alkaliphiles evolved mechanisms that solve these
challenges. The monovalent cation/proton antiporters which exchange the intracellular cations such as Na
+ and Li
+ for the extracellular H
+ are believed to be the most
important mechanism that alkaliphiles depend on for intracellular pH homeostasis
[21, 52–59]. Based on the Transporter Classification Database (TCDB; http://www.
tcdb.org), these antiporters are diverse and belong to two superfamilies. The cation/
proton antiporters (CPA) superfamily which consists of five families including
family CPA1 and CPA2 and the Na
+ transporting Mrp superfamily that comprises
three families including family CPA3 which is among the most vital H
+ translocating
antiporters of alkaliphiles [22, 60]. In addition to the families that belong to the
two superfamilies, the Nha families, NhaA, NhaB, NhaC, and NhaD [61] are also
involved in the homeostasis process [62].
Among the monovalent cation/proton antiporters, Na
+
/H
+ antiporters which
exchange cytoplasmic Na
+ for extracellular H
+ seem to be very crucial for pH
homeostasis in alkaliphiles [21, 22, 54, 55]. Moreover, these antiporters are also
used for Na
+ and volume homeostasis as well, like what it does in eukaryotic cells
and their organelles [58, 63–66]. These antiporters avoid the accumulation of Na
+ to
toxic level, while it maintains relatively higher H
+ concentration in the cytoplasm
[21, 67]. The Na
+
/H
+ antiporters are secondary active transporters which use the
transmembrane electrical potential (Δψ) generated by primary ion pumps such as
the respiratory complexes [27] to efflux intracellular Na
+ [21, 54, 55, 68, 69]. In
alkaliphiles, the monovalent cation/proton antiporter-mediated pH homeostasis is
primarily specific for Na
+ but also accommodates Li
+ efflux. On the other hand,
unlike alkaliphiles, neutralophiles use not only Na
+
(Li
+ )/H
+ antiporters but also K
+
/
H
+ antiporters [21, 22]. The specificity of the alkaliphiles monovalent cation/proton
antiporters system to Na
+ is believed to avoid severe depletion of cytoplasmic K
+
that can potentially compromise some cytoplasmic processes [21] and enhances the
cytotoxicity of Na
+ [21, 70, 71]. The other possibility might be that most of the
studied alkaliphiles are adapted to habitats such as soda lakes with high level of Na
+
;
hence, it is ideal for such organisms to evolve a system that relies on the ample
resource (Na
+ ).
Comparative analysis of genes encoding CPAs in genomes of alkaliphiles and
neutralophiles revealed that there is no significant difference in the number of the
genes between alkaliphiles and neutralophiles [54, 55]. However, the aggregate level
of the Na
+
/H
+ antiporter is much higher in alkaliphiles than in neutralophiles [21, 52,
53, 72]. This may be due to the greater burden of pH homeostasis at higher
94
G. Mamo