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The different facets of organelle interplay-an overview of organelle interactions.

Schrader M, Godinho LF, Costello JL, Islinger M - Front Cell Dev Biol (2015)

Bottom Line: Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level.Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy-a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling.This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, College of Life and Environmental Sciences, University of Exeter Exeter, UK.

ABSTRACT
Membrane-bound organelles such as mitochondria, peroxisomes, or the endoplasmic reticulum (ER) create distinct environments to promote specific cellular tasks such as ATP production, lipid breakdown, or protein export. During recent years, it has become evident that organelles are integrated into cellular networks regulating metabolism, intracellular signaling, cellular maintenance, cell fate decision, and pathogen defence. In order to facilitate such signaling events, specialized membrane regions between apposing organelles bear distinct sets of proteins to enable tethering and exchange of metabolites and signaling molecules. Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level. However, historical and recent observations imply that other organelles like peroxisomes, lysosomes, and lipid droplets might also be involved in the formation of such apposing membrane contact sites. Alternatively, reports on so-called mitochondria derived-vesicles (MDV) suggest alternative mechanisms of organelle interaction. Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy-a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling. This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.

No MeSH data available.


Schematic overview of proteins and lipids involved in the interaction of organelles. (A) Tethering complexes in mammals: unlike in yeast species only a few protein complexes have been characterized at the molecular level and involve protein-protein and protein-lipid contacts [see Sections Connections between the ER and the Plasma Membrane, The Mitochondria-associated Membrane of the ER (MAM), Interplay between Peroxisomes and Mitochondria, and Lysosomal Interactions and Autophagy]. Part of the tethering complexes shown may only comprise core complexes, which will interact with additional proteins for regulatory purposes; (B) contacts between mitochondria/peroxisomes and the autophagosomal membrane: both organelles require ubiquitination of membrane proteins for recognition by the autophagosome. In addition to MFN2 (Mitochondria) and Pex5 (Peroxisomes) other ubiquitinated organelle proteins have been described to participate in autophagosomal contacts [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Lysosomal Interactions and Autophagy]; (C) ERMES as a multifunctional tethering complex in yeast: unlike mammals, yeast species possess the ERMES oligomeric complex at the mitochondrial membrane. ERMES forms complexes with the ER and peroxisomes [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria]. In addition, a considerable number of other tethering complexes (not shown) have been described in yeast (Prinz, 2014). For molecular details and references of the depicted complexes please refer to the corresponding sections of this review. Membrane spanning α-helices in the proteins are depicted as cylindrical segments; C- and N-termini are marked with the corresponding letters.
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Figure 2: Schematic overview of proteins and lipids involved in the interaction of organelles. (A) Tethering complexes in mammals: unlike in yeast species only a few protein complexes have been characterized at the molecular level and involve protein-protein and protein-lipid contacts [see Sections Connections between the ER and the Plasma Membrane, The Mitochondria-associated Membrane of the ER (MAM), Interplay between Peroxisomes and Mitochondria, and Lysosomal Interactions and Autophagy]. Part of the tethering complexes shown may only comprise core complexes, which will interact with additional proteins for regulatory purposes; (B) contacts between mitochondria/peroxisomes and the autophagosomal membrane: both organelles require ubiquitination of membrane proteins for recognition by the autophagosome. In addition to MFN2 (Mitochondria) and Pex5 (Peroxisomes) other ubiquitinated organelle proteins have been described to participate in autophagosomal contacts [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Lysosomal Interactions and Autophagy]; (C) ERMES as a multifunctional tethering complex in yeast: unlike mammals, yeast species possess the ERMES oligomeric complex at the mitochondrial membrane. ERMES forms complexes with the ER and peroxisomes [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria]. In addition, a considerable number of other tethering complexes (not shown) have been described in yeast (Prinz, 2014). For molecular details and references of the depicted complexes please refer to the corresponding sections of this review. Membrane spanning α-helices in the proteins are depicted as cylindrical segments; C- and N-termini are marked with the corresponding letters.

Mentions: In eukaryotic cells sophisticated membrane-bound organelles have evolved which enable the cell to compartmentalize specialized biochemical reactions in specific locations within the cell (Figure 1). Historically, subcellular compartments were regarded as isolated, membrane bound biochemical entities, and individual organelles such as mitochondria, lysosomes, peroxisomes, or the endoplasmic reticulum (ER) have been associated with distinct cellular tasks including ATP production, protein degradation, lipid breakdown, and protein export. In recent years, a combination of ultrastructural studies, fluorescence-based live cell imaging techniques, molecular cell biology, biochemistry, and modern proteomics approaches has substantially changed this view towards a highly dynamic, cooperative and complex network of interacting and communicating subcellular compartments (Figure 1). It is evident that intracellular compartments have to exchange material and transmit signals between each other to maintain and balance cellular activities. Cooperative functions of organelle networks include (1) metabolic interaction, (2) intracellular signaling, (3) cellular maintenance, (4) regulation of programmed cell death/cell survival, and (5) pathogen defence. Mechanistically, functional interplay can be established by vesicular transport (as initially revealed for organelles within the secretory pathway), by exchange of metabolites or signaling molecules through diffusion, or direct physical contacts which are mediated by specialized membrane contact sites (Figure 2). It is becoming evident that the cytoskeleton and molecular motors are not the sole organizers of cellular architecture, and that membrane contacts can influence the positioning and motility of organelles. Organelle interaction also depends on the total number of organelles which is regulated by organelle biogenesis/formation, membrane dynamics and autophagic processes. Remarkably, these processes also involve membrane contact sites, for example ER-mitochondria contacts which are supposed to contribute to mitochondrial division [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria] or interactions with lysosomes during autophagy (see Section Lysosomal Interactions and Autophagy). Membrane contact sites involve tethering of two membranes in close apposition (typically within 30 nm) and the enrichment of specific proteins and/or lipids at these sites (see Table 1). In general, the tethered membranes do not fuse, but contact formation has an impact on the function or composition of one or both organelles. Although membrane contacts between organelles have been reported in early ultrastructural studies, their important functions in intracellular signaling, metabolite transport/metabolism, organelle dynamics and transport is just beginning to emerge. Furthermore, a growing number of proteins with potential tethering functions are being identified in yeast and mammals.


The different facets of organelle interplay-an overview of organelle interactions.

Schrader M, Godinho LF, Costello JL, Islinger M - Front Cell Dev Biol (2015)

Schematic overview of proteins and lipids involved in the interaction of organelles. (A) Tethering complexes in mammals: unlike in yeast species only a few protein complexes have been characterized at the molecular level and involve protein-protein and protein-lipid contacts [see Sections Connections between the ER and the Plasma Membrane, The Mitochondria-associated Membrane of the ER (MAM), Interplay between Peroxisomes and Mitochondria, and Lysosomal Interactions and Autophagy]. Part of the tethering complexes shown may only comprise core complexes, which will interact with additional proteins for regulatory purposes; (B) contacts between mitochondria/peroxisomes and the autophagosomal membrane: both organelles require ubiquitination of membrane proteins for recognition by the autophagosome. In addition to MFN2 (Mitochondria) and Pex5 (Peroxisomes) other ubiquitinated organelle proteins have been described to participate in autophagosomal contacts [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Lysosomal Interactions and Autophagy]; (C) ERMES as a multifunctional tethering complex in yeast: unlike mammals, yeast species possess the ERMES oligomeric complex at the mitochondrial membrane. ERMES forms complexes with the ER and peroxisomes [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria]. In addition, a considerable number of other tethering complexes (not shown) have been described in yeast (Prinz, 2014). For molecular details and references of the depicted complexes please refer to the corresponding sections of this review. Membrane spanning α-helices in the proteins are depicted as cylindrical segments; C- and N-termini are marked with the corresponding letters.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Schematic overview of proteins and lipids involved in the interaction of organelles. (A) Tethering complexes in mammals: unlike in yeast species only a few protein complexes have been characterized at the molecular level and involve protein-protein and protein-lipid contacts [see Sections Connections between the ER and the Plasma Membrane, The Mitochondria-associated Membrane of the ER (MAM), Interplay between Peroxisomes and Mitochondria, and Lysosomal Interactions and Autophagy]. Part of the tethering complexes shown may only comprise core complexes, which will interact with additional proteins for regulatory purposes; (B) contacts between mitochondria/peroxisomes and the autophagosomal membrane: both organelles require ubiquitination of membrane proteins for recognition by the autophagosome. In addition to MFN2 (Mitochondria) and Pex5 (Peroxisomes) other ubiquitinated organelle proteins have been described to participate in autophagosomal contacts [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Lysosomal Interactions and Autophagy]; (C) ERMES as a multifunctional tethering complex in yeast: unlike mammals, yeast species possess the ERMES oligomeric complex at the mitochondrial membrane. ERMES forms complexes with the ER and peroxisomes [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria]. In addition, a considerable number of other tethering complexes (not shown) have been described in yeast (Prinz, 2014). For molecular details and references of the depicted complexes please refer to the corresponding sections of this review. Membrane spanning α-helices in the proteins are depicted as cylindrical segments; C- and N-termini are marked with the corresponding letters.
Mentions: In eukaryotic cells sophisticated membrane-bound organelles have evolved which enable the cell to compartmentalize specialized biochemical reactions in specific locations within the cell (Figure 1). Historically, subcellular compartments were regarded as isolated, membrane bound biochemical entities, and individual organelles such as mitochondria, lysosomes, peroxisomes, or the endoplasmic reticulum (ER) have been associated with distinct cellular tasks including ATP production, protein degradation, lipid breakdown, and protein export. In recent years, a combination of ultrastructural studies, fluorescence-based live cell imaging techniques, molecular cell biology, biochemistry, and modern proteomics approaches has substantially changed this view towards a highly dynamic, cooperative and complex network of interacting and communicating subcellular compartments (Figure 1). It is evident that intracellular compartments have to exchange material and transmit signals between each other to maintain and balance cellular activities. Cooperative functions of organelle networks include (1) metabolic interaction, (2) intracellular signaling, (3) cellular maintenance, (4) regulation of programmed cell death/cell survival, and (5) pathogen defence. Mechanistically, functional interplay can be established by vesicular transport (as initially revealed for organelles within the secretory pathway), by exchange of metabolites or signaling molecules through diffusion, or direct physical contacts which are mediated by specialized membrane contact sites (Figure 2). It is becoming evident that the cytoskeleton and molecular motors are not the sole organizers of cellular architecture, and that membrane contacts can influence the positioning and motility of organelles. Organelle interaction also depends on the total number of organelles which is regulated by organelle biogenesis/formation, membrane dynamics and autophagic processes. Remarkably, these processes also involve membrane contact sites, for example ER-mitochondria contacts which are supposed to contribute to mitochondrial division [see Sections The Mitochondria-associated Membrane of the ER (MAM) and Interplay between Peroxisomes and Mitochondria] or interactions with lysosomes during autophagy (see Section Lysosomal Interactions and Autophagy). Membrane contact sites involve tethering of two membranes in close apposition (typically within 30 nm) and the enrichment of specific proteins and/or lipids at these sites (see Table 1). In general, the tethered membranes do not fuse, but contact formation has an impact on the function or composition of one or both organelles. Although membrane contacts between organelles have been reported in early ultrastructural studies, their important functions in intracellular signaling, metabolite transport/metabolism, organelle dynamics and transport is just beginning to emerge. Furthermore, a growing number of proteins with potential tethering functions are being identified in yeast and mammals.

Bottom Line: Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level.Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy-a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling.This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, College of Life and Environmental Sciences, University of Exeter Exeter, UK.

ABSTRACT
Membrane-bound organelles such as mitochondria, peroxisomes, or the endoplasmic reticulum (ER) create distinct environments to promote specific cellular tasks such as ATP production, lipid breakdown, or protein export. During recent years, it has become evident that organelles are integrated into cellular networks regulating metabolism, intracellular signaling, cellular maintenance, cell fate decision, and pathogen defence. In order to facilitate such signaling events, specialized membrane regions between apposing organelles bear distinct sets of proteins to enable tethering and exchange of metabolites and signaling molecules. Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level. However, historical and recent observations imply that other organelles like peroxisomes, lysosomes, and lipid droplets might also be involved in the formation of such apposing membrane contact sites. Alternatively, reports on so-called mitochondria derived-vesicles (MDV) suggest alternative mechanisms of organelle interaction. Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy-a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling. This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.

No MeSH data available.