Role of exosomes in the protection of cellular homeostasis

Desdín-Micó, Gabriela; Mittelbrunn, Marı́a

doi:10.1080/19336918.2016.1251000

Cited by 144 publications

(106 citation statements)

References 85 publications

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“…Indeed, MDVs are generated also in cells lacking autophagy-related serine/threonine kinase gene (Atg) 5, Beclin-1, or RAB9, as well as after DRP1-silencing [67]. Thus, MDV generation and delivery are thought to complement mitophagy for MQC when mitochondrial damage is mild or when mitophagy is overwhelmed or compromised [69]. The presence of mitochondrial constituents within exosomes is itself an indirect evidence of crosstalk between mitochondria and the endolysosomal system [70,71].…”

Section: Generation and Release Of Mitochondrial Derived Vesiclesmentioning

confidence: 99%

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

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Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca 2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson's disease as a prototypical geroscience condition.Cells 2020, 9, 598 2 of 18 instability, telomere attrition, epigenetic alterations, deregulated nutrient sensing, and stem cell exhaustion [3]. According to the geroscience hypothesis, perturbations in these mechanisms increase the susceptibility to most chronic diseases, functional loss, and eventually, death [4]. Hence, these biologic pillars represent ideal targets for interventions to foster healthy aging [5,6].Mitochondrial dysfunction has attracted considerable interest as a target for geroprotective interventions. Indeed, mitochondria play sensor-transducer-effector roles in a multitude of biological processes, including integration of cell death signaling and preservation of cell stemness [7,8]. Albeit long considered to be standalone organelles, a great deal of evidence indicates that mitochondria interact physically and functionally with other cellular compartments via membrane contact sites and tethering molecules [9,10]. In particular, mitochondria establish connections with the endosomal compartment [11,12] and lysosomes [13,14]. These interactions support cytosolic shuttle systems of ions and metabolites across organelles [10,15], and participate to the regulation of cellular housekeeping processes [13,14].The mitochondrial-lysosomal axis is a major actor in mitochondrial quality control (MQC), a hierarchical network of pathways that ensure organellar homeostasis through the coordination of mitochondrial proteostasis, dynamics, biogene...

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Section: Generation and Release Of Mitochondrial Derived Vesiclesmentioning

confidence: 99%

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

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Section: Exosomes In Sequential Processes Of Tumor Metastasismentioning

confidence: 99%

“…On one hand, the crosstalk between exosomes and the different cellular degradation mechanisms confers an additional layer of protection to maintain cellular integrity and homeostasis in a number of physiological and pathological conditions. 100 On the other hand, exosomes especially platelet-derived ones play important roles in protecting CTCs. 101 Except for inducing the platelet activation and aggregation in direct manners, tumor cells can shed exosomes that expose the transmembrane protein tissue factors, the initiator of the extrinsic coagulation cascade.…”

Section: Exosomal Integrin Model Only Until 2015 Hoshino Et Almentioning

confidence: 99%

Exosomes play roles in sequential processes of tumor metastasis

Chen

et al. 2018

Intl Journal of Cancer

141

105

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Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.

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“…Multivesicular bodies can either be directed to lysosomes for degradation or transported to the plasma membrane for exosome release . Thus, exosomes were a protein quality control pathway in addition to degradation‐based approach, maintaining protein homeostasis by exporting misfolded proteins through excretion route . Autophagy is another pathway in the maintenance of protein homeostasis and the preservation of proper organelle function by selective removal of damaged organelles.…”

Section: Biological Functions Of Evsmentioning

confidence: 99%

“…10 Thus, exosomes were a protein quality control pathway in addition to degradation-based approach, maintaining protein homeostasis by exporting misfolded proteins through excretion route. 11 Autophagy is another pathway in the maintenance of protein homeostasis and the preservation of proper organelle function by selective removal of damaged organelles. Under conditions that stimulate autophagy, MVBs are directed to the autophagic pathway that consequently inhibits exosome release.…”

Section: Evs Were Released To Maintain Cell Homeostasismentioning

confidence: 99%

New insight into the role of extracellular vesicles in kidney disease

Feng

Tang

et al. 2018

J Cellular Molecular Medi

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Extracellular vesicles (EVs) are released to maintain cellular homeostasis as well as to mediate cell communication by spreading protective or injury signals to neighbour or remote cells. In kidney, increasing evidence support that EVs are signalling vesicles for different segments of tubules, intra‐glomerular, glomerular‐tubule and tubule‐interstitial communication. EVs released by kidney resident and infiltrating cells can be isolated from urine and were found to be promising biomarkers for kidney disease, reflecting deterioration of renal function and histological change. We have here summarized the recent progress about the functional role of EVs in kidney disease as well as challenges and future directions involved.

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Role of exosomes in the protection of cellular homeostasis

Cited by 144 publications

References 85 publications

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Exosomes play roles in sequential processes of tumor metastasis

New insight into the role of extracellular vesicles in kidney disease

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