Organelle communication: Signaling crossroads between homeostasis and disease

Bravo-Sagua, Roberto; Torrealba, Natalia; Paredes, Felipe; Morales, Pablo E.; Pennanen, Christian; López-Crisosto, Camila; Troncoso, Rodrigo; Criollo, Alfredo; Chiong, Mario; Hill, Joseph A.; Simmen, Thomas; Quest, Andrew F. G.; Lavandero, Sergio

doi:10.1016/j.biocel.2014.01.019

Cited by 49 publications

(30 citation statements)

References 41 publications

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“…This early evidence for the existence of physical ER-mitochondria interactions led to the genesis of the term MAM, standing for Mitochondria-associated ER membranes [11]. Ever since their discovery, the importance of these contact sites in organelle cross-talk has been confirmed using numerous approaches ( Figure 1) [4][5][6]12].…”

Section: Introductionmentioning

confidence: 97%

“…Although this division is essential for separating potentially incompatible activities, regulated integration of cellular physiology depends upon effective cross-talk and functional coordination between multiple organelles [4][5][6]. Such inter-organelle communication is frequently achieved by direct physical contact between organellar membranes and the necessary interactions are often highly regulated as well as dynamic in time and space [4][5][6][7]. One of the best characterized such interorganellar communication sites are the connections between the endoplasmic reticulum (ER) and mitochondria.…”

Section: Introductionmentioning

confidence: 99%

“…ER-mitochondria contact sites permit reciprocal regulation of function in both organelles, thereby impacting various cellular activities, including energy metabolism, Ca 2+ handling [13], lipid homeostasis [9] as well as regulation of cell death and survival [4][5][6][7]. In this review, we highlight the role of a number of proteins important in regulating the ER-mitochondria interface,…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ER-to-mitochondria miscommunication and metabolic diseases

López-Crisosto

Bravo-Sagua

Rodriguez–Peña

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Eukaryotic cells contain a variety of subcellular organelles, each of which performs unique tasks. Thus follows that in order to coordinate these different intracellular functions, a highly dynamic system of communication must exist between the various compartments. Direct endoplasmic reticulum (ER)-mitochondria communication is facilitated by the physical interaction of their membranes in dedicated structural domains known as mitochondria-associated membranes (MAMs), which facilitate calcium (Ca(2+)) and lipid transfer between organelles and also act as platforms for signaling. Numerous studies have demonstrated the importance of MAM in ensuring correct function of both organelles, and recently MAMs have been implicated in the genesis of various human diseases. Here, we review the salient structural features of interorganellar communication via MAM and discuss the most common experimental techniques employed to assess functionality of these domains. Finally, we will highlight the contribution of MAM to a variety of cellular functions and consider the potential role of MAM in the genesis of metabolic diseases. In doing so, the importance for cell functions of maintaining appropriate communication between ER and mitochondria will be emphasized.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ER-to-mitochondria miscommunication and metabolic diseases

López-Crisosto

Bravo-Sagua

Rodriguez–Peña

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Indeed, a growing body of evidence indicates that a defect in inter-organelle communication may play a role in the pathogenesis of multiple human diseases (30,33,59,60). More specifically, abnormalities associated with EMCs have been reported to be linked to multiple neurodegenerative disorders (20,30,61).…”

Section: Rtn1a Promotes Er-mitochondrial Contactsmentioning

confidence: 99%

Ascorbate peroxidase proximity labeling coupled with biochemical fractionation identifies promoters of endoplasmic reticulum–mitochondrial contacts

Cho

Adelmant

Lim

et al. 2017

Journal of Biological Chemistry

100

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Edited by John M. DenuTo maintain cellular homeostasis, subcellular organelles communicate with each other and form physical and functional networks through membrane contact sites coupled by protein tethers. In particular, endoplasmic reticulum (ER)-mitochondrial contacts (EMC) regulate diverse cellular activities such as metabolite exchange (Ca 2؉ and lipids), intracellular signaling, apoptosis, and autophagy. The significance of EMCs has been highlighted by reports indicating that EMC dysregulation is linked to neurodegenerative diseases. Therefore, obtaining a better understanding of the physical and functional components of EMCs should provide new insights into the pathogenesis of several neurodegenerative diseases. Here, we applied engineered ascorbate peroxidase (APEX) to map the proteome at EMCs in live HEK293 cells. APEX was targeted to the outer mitochondrial membrane, and proximity-labeled proteins were analyzed by stable isotope labeling with amino acids in culture (SILAC)-LC/MS-MS. We further refined the specificity of the proteins identified by combining biochemical subcellular fractionation to the protein isolation method. We identified 405 proteins with a 2.0-fold cutoff ratio (log base 2) in SILAC quantification from replicate experiments. We performed validation screening with a Split-Rluc8 complementation assay that identified reticulon 1A (RTN1A), an ER-shaping protein localized to EMCs as an EMC promoter. Proximity mapping augmented with biochemical fractionation and additional validation methods reported here could be useful to discover other components of EMCs, identify mitochondrial contacts with other organelles, and further unravel their communication.

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“…Endoplasmic reticulum (ER) and mitochondria are profoundly interdependent organelles123. Protein folding in the ER, for instance, is a highly energy-demanding process that requires large amounts of ATP, which are provided by mitochondria4.…”

mentioning

confidence: 99%

mTORC1 inhibitor rapamycin and ER stressor tunicamycin induce differential patterns of ER-mitochondria coupling

Bravo-Sagua

López-Crisosto

Parra

et al. 2016

Sci Rep

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Efficient mitochondrial Ca2+ uptake takes place at contact points between the ER and mitochondria, and represents a key regulator of many cell functions. In a previous study with HeLa cells, we showed that ER-to-mitochondria Ca2+ transfer increases during the early phase of ER stress induced by tunicamycin as an adaptive response to stimulate mitochondrial bioenergetics. It remains unknown whether other types of stress signals trigger similar responses. Here we observed that rapamycin, which inhibits the nutrient-sensing complex mTORC1, increased ER-mitochondria coupling in HeLa cells to a similar extent as did tunicamycin. Interestingly, although global responses to both stressors were comparable, there were notable differences in the spatial distribution of such changes. While tunicamycin increased organelle proximity primarily in the perinuclear region, rapamycin increased organelle contacts throughout the entire cell. These differences were paralleled by dissimilar alterations in the distribution of regulatory proteins of the ER-mitochondria interface, heterogeneities in mitochondrial Ca2+ uptake, and the formation of domains within the mitochondrial network with varying mitochondrial transmembrane potential. Collectively, these data suggest that while increasing ER-mitochondria coupling appears to represent a general response to cell stress, the intracellular distribution of the associated responses needs to be tailored to meet specific cellular requirements.

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Organelle communication: Signaling crossroads between homeostasis and disease

Cited by 49 publications

References 41 publications

ER-to-mitochondria miscommunication and metabolic diseases

ER-to-mitochondria miscommunication and metabolic diseases

Ascorbate peroxidase proximity labeling coupled with biochemical fractionation identifies promoters of endoplasmic reticulum–mitochondrial contacts

mTORC1 inhibitor rapamycin and ER stressor tunicamycin induce differential patterns of ER-mitochondria coupling

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