Subject: CBB seminar April 29

NCBI CBB seminar, Tuesday April 29, 11:00 am, B2 library

The choice between proton- and sodium ion-based membrane energetics in bacteria

Michael Y. Galperin

Joint work with Eugene Koonin, Kira Makarova, Yuri Wolf, and Armen Mulkidjanian.

All living cells routinely accumulate K+ ions and expel Na+ ions, maintaining lower concentration of Na+ in the cytoplasm than in the surrounding milieu.
  My diploma project in 1978/79 analyzed the roles of transmembrane gradients of Na+ and K+ ions in membrane bioenergetics and concluded that these 
gradients served to buffer the magnitude of the transmembrane electrochemical gradient of H+ ions (proton-motive force, PMF) [1]. Indeed, in the vast
 majority of bacteria, as well as in mitochondria and chloroplasts, export of Na+ occurs at the expense of the PMF. However, some bacteria and archaea
 possess primary Na+ ion pumps that generate transmembrane electrochemical gradient of Na+ (sodium-motive force, SMF) independently of the PMF. In 
the past 30 years, several hypotheses on the roles of these ion gradients were put forward, suggesting that primary Na+ pumps were adaptations of 
extremophilic bacteria to high external pH (V.P. Skulachev) or to high temperature (W.N. Konings). However, we and others were able to detect genes 
for primary Na+ pumps in a variety of non-extremophiles, such as marine bacteria and certain bacterial pathogens [2]. Further, many alkaliphiles 
and hyperthermophiles were shown to rely on H+, not Na+, as the coupling ion. We have concluded that the SMF was used by bacteria primarily in anaerobic 
conditions, whereas aerobes used the PMF.  

The recent structural characterization of the Na+-binding sites in the membrane subunits of F- and V-type ATP synthases allowed us to re-examine this 
issue, based on the confident prediction of the ion specificity of these enzymes encoded in a variety of recently sequenced microbial genomes. Our analysis 
shows that, contrary to the common view, utilization of Na+- or H+-translocating ATPases does not directly correlate with thermophily or alkalophily 
of the organism. Instead, Na+ serves as the coupling ion in obligate anaerobes, both bacterial and archaeal, that are unable to use alternative electron 
acceptors, whereas thermo- and alkaliphiles that are capable of utilizing nitrate, sulfite, arsenate, or metal ions as terminal electron acceptors 
typically rely on the PMF [3]. The distribution of Na+- or H+-dependent enzymes indicates that the SMF-based Na+ ion cycle was the first to emerge 
in evolution but was later replaced by the H+ cycle in most aerobic and facultatively anaerobic organisms [4]. The conclusion on evolutionary primacy 
of the SMF leads to interesting insights into the origin of contemporary membranes. It also leads to a better understanding of the mechanisms, 
evolutionary advantages and limitations of switching from Na+ to H+ as the coupling ion and the possible reasons why certain pathogenic bacteria 
still rely on the SMF.

1. Brown II, Galperin MY, Glagolev AN, Skulachev VP (1983) Eur. J. Biochem.  134: 345-349. PMID: 6307692

2. Häse CC, Fedorova ND, Galperin MY, Dibrov PA (2001) Microbiol. Mol. Biol. Rev. 65: 353-370. PMID: 11528000

3. Mulkidjanian AY, Dibrov P., Galperin MY (2008) Biochim. Biophys. Acta,  in press

4. Mulkidjanian AY, Galperin MY, Makarova KS, Wolf YI, Koonin EV. (2008) Biol Direct. 3:13. PMID: 18380897