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Membrane fusion induced by small molecules and ions.

Mondal Roy S, Sarkar M - J Lipids (2011)

Bottom Line: Small molecules/ions do not share this advantage.Here we intend to present, how a variety of small molecules/ions act as independent fusogens.The detailed mechanism of some are well understood but for many it is still an unanswered question.

View Article: PubMed Central - PubMed

Affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, Sector 1, Block AF, Bidhannagar, Kolkata 700064, India.

ABSTRACT
Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes.

No MeSH data available.


Related in: MedlinePlus

Basic Steps of membrane fusion. (a) Membrane contact, (b) outer leaflet lipid mixing to form the hemifused state, and (c) inner leaflet lipid mixing and pore formation and content mixing.
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fig1: Basic Steps of membrane fusion. (a) Membrane contact, (b) outer leaflet lipid mixing to form the hemifused state, and (c) inner leaflet lipid mixing and pore formation and content mixing.

Mentions: The process of membrane fusion varies widely in different systems. For example, fusion of yeast vacuoles (dimension-micron level) occur through an area of contact, which is almost 10000-fold larger compared to that during exocytosis of synaptic vesicles. Whereas, the vacuoles take minutes to undergo fusion, the synaptic vesicles take milliseconds, which means ∼10000-fold shorter times than yeast vacuoles [9]. Fusion both in vivo and in vitro is usually induced by external agents called fusogens. The most common fusogens are large molecules like proteins and peptides. There are also other types of fusogens which will be detailed later in the text. Depending on the nature of the fusogens, the exact mechanism varies. By “mechanism,” we mean the way a fusogenic agent will induce the fusion process. Despite the diversities in the mechanism, the process is characterized by similar basic steps in all kinds of membrane fusion (Figure 1). In order to fuse two membranes, they must first be brought together such that their surfaces become closely apposed. This requires removal of aqueous environment associated with the polar head groups and is expected to be one of the most energetically demanding process [10]. This is followed by a local disruption of the organized bilayer which results in fusion of outer leaflet of each membrane forming the hemifused, often “stalk-like” intermediate. Next, reorganization of the inner lipid leaflet results in pore opening and mixing of inner aqueous contents to complete the fusion process. Each intermediate state of the fusion process is characterized by their specific conformational energy which is the associated potential energy of the state. The difference in the conformational energy between state 2 and state 1 provides the potential energy barrier. This needs to be overcome for the fusion to proceed. A fusogen provides this energy to overcome the barrier which is translated into the required kinetic energy that drives the membrane from one intermediate step to the next by structural reorganization of the lipid molecules in the bilayer. If the amount of energy supplied by the fusogens is not enough to strike the correct “structure energy balance,” that is, the energy supplied is not adequate to form the correct structure of the next intermediate, the fusion process will not be able to proceed further.


Membrane fusion induced by small molecules and ions.

Mondal Roy S, Sarkar M - J Lipids (2011)

Basic Steps of membrane fusion. (a) Membrane contact, (b) outer leaflet lipid mixing to form the hemifused state, and (c) inner leaflet lipid mixing and pore formation and content mixing.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108104&req=5

fig1: Basic Steps of membrane fusion. (a) Membrane contact, (b) outer leaflet lipid mixing to form the hemifused state, and (c) inner leaflet lipid mixing and pore formation and content mixing.
Mentions: The process of membrane fusion varies widely in different systems. For example, fusion of yeast vacuoles (dimension-micron level) occur through an area of contact, which is almost 10000-fold larger compared to that during exocytosis of synaptic vesicles. Whereas, the vacuoles take minutes to undergo fusion, the synaptic vesicles take milliseconds, which means ∼10000-fold shorter times than yeast vacuoles [9]. Fusion both in vivo and in vitro is usually induced by external agents called fusogens. The most common fusogens are large molecules like proteins and peptides. There are also other types of fusogens which will be detailed later in the text. Depending on the nature of the fusogens, the exact mechanism varies. By “mechanism,” we mean the way a fusogenic agent will induce the fusion process. Despite the diversities in the mechanism, the process is characterized by similar basic steps in all kinds of membrane fusion (Figure 1). In order to fuse two membranes, they must first be brought together such that their surfaces become closely apposed. This requires removal of aqueous environment associated with the polar head groups and is expected to be one of the most energetically demanding process [10]. This is followed by a local disruption of the organized bilayer which results in fusion of outer leaflet of each membrane forming the hemifused, often “stalk-like” intermediate. Next, reorganization of the inner lipid leaflet results in pore opening and mixing of inner aqueous contents to complete the fusion process. Each intermediate state of the fusion process is characterized by their specific conformational energy which is the associated potential energy of the state. The difference in the conformational energy between state 2 and state 1 provides the potential energy barrier. This needs to be overcome for the fusion to proceed. A fusogen provides this energy to overcome the barrier which is translated into the required kinetic energy that drives the membrane from one intermediate step to the next by structural reorganization of the lipid molecules in the bilayer. If the amount of energy supplied by the fusogens is not enough to strike the correct “structure energy balance,” that is, the energy supplied is not adequate to form the correct structure of the next intermediate, the fusion process will not be able to proceed further.

Bottom Line: Small molecules/ions do not share this advantage.Here we intend to present, how a variety of small molecules/ions act as independent fusogens.The detailed mechanism of some are well understood but for many it is still an unanswered question.

View Article: PubMed Central - PubMed

Affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, Sector 1, Block AF, Bidhannagar, Kolkata 700064, India.

ABSTRACT
Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes.

No MeSH data available.


Related in: MedlinePlus