Linkage Between Membrane Composition, Cellular Functions and Membrane- Mediated Stress

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Background

Biological membranes are vital for maintaining cell integrity and function. The proteome, which includes transmembrane and peripheral membrane proteins in addition to the lipidome, determines the functional characteristics of cell membranes. The association between a membrane protein (both integral and peripheral membrane) and lipids, in particular, the acidic phospholipids such as phosphatidylglycerol (PG) and cardiolipin (CL) present in the fluid bilayer are linked with the regulation of critical cellular functions, including acidic phospholipid-induced apoptosis in mitochondria, oxidative phosphorylation, and regulation of respiratory complexes in both the yeast and bacteria. Studying how cellular membrane composition influences the function of integral and peripheral membrane proteins to cause significant disruption of important cellular functions could be very useful to broaden knowledge on the impact membranes have on critical cellular events as well as to develop new antibiotic strategies.

Accumulating evidence indicates that acidic phospholipids present in the bacterial inner membranes are involved in the chromosomal and cell division-related events such as initiation of DNA replication. For instance, the role of cellular membranes particularly in Escherichia coli has long been hypothesized in controlling the process of initiation of replication. Genetic evidences in concert with various biochemical studies indicate that the cellular membranes might modulate the initiator activity of E. coli chromosomal replication initiator protein, DnaA, which mediates the process of replication initiation when it binds to specific recognition elements present within the chromosomal origin oriC, but only in an adenine nucleotide-dependent manner. In addition, consensus sequences for DnaA binding are located throughout the E. coli genome, including within promoter regions of several genes, such as rpoH, mioC, nrdAB, and dnaA itself, and thus is also known as master transcriptional regulator protein. Moreover crosslinking, cytolocalization and immunofluorescence studies revealed the peripheral association between DnaA and acidic membrane present in bacterial inner membranes.

However, an important question that needs to be addressed is how changes in the membrane composition adversely affect the cellular processes and causes cellular toxicity, and how is it linked to perturbed protein-membrane interaction? Although limited available knowledge about DnaA-membrane association comes mostly from gram-negative commensal bacteria E. coli, the overall process of initiation of replication is evolutionary conserved in bacteria including gram-negative, gram-positive, non pathogenic or pathogenic bacteria. Moreover the eukaryotic protein orC1p or Cdc6 is a structural and functional homolog of bacterial DnaA protein, indicating a possible parallelism of this process in higher organisms.

In this Research Topic, we invite articles that should provide an understanding of mechanisms allowing the bacterial cells carrying altered membrane content to survive, and evade any membrane-mediated stress affecting critical cellular functions. These include studies in bacterial cells carrying perturbed acidic phospholipid composition and its related impact on the (i) global expression profiles determined at the RNA or protein level; (ii) alteration of metagenomic, metatranscriptomic or metaproteomic profiles in bacteria; (iii) genome structure, which may result in the genetic instability in bacteria. The studies submitted in this issue could execute interesting approaches but not limited to (i) advances in genome sequencing approaches relevant to bacteria, including single-cell methods; (ii) synthetic genomics and metabolic engineering; (iii) new or improved tools for the analysis of genomes in the absence of normal cellular membrane composition.

Keywords: Membrane composition, peripheral proteins, integral protein, acidic phospholipids, membrane-protein association

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