Endoplasmic Reticulum–Mitochondria Contact Sites—Emerging Intracellular Signaling Hubs

Aoyama-Ishiwatari, Saeko; Hirabayashi, Yusuke

doi:10.3389/fcell.2021.653828

Cited by 40 publications

(36 citation statements)

References 101 publications

(115 reference statements)

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“…The fourth type are ERresident proteins that are enriched in MAMs where they regulate several ER functions, such as calnexin or calbindin (Wieckowski et al, 2009). For comprehensive reviews, see Aoyama-Ishiwatari and Hirabayashi (2021) and Csordas et al (2018). (1) Regulation of Ca 2+ homeostasis is a key function of ERmitochondria signaling in neurons.…”

Section: Er-mitochondria Tethering Proteins In Neuronsmentioning

confidence: 99%

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Markovinović

Greig

Martín‐Guerrero

et al. 2022

Journal of Cell Science

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Recent advances have revealed common pathological changes in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis with related frontotemporal dementia (ALS/FTD). Many of these changes can be linked to alterations in endoplasmic reticulum (ER)–mitochondria signaling, including dysregulation of Ca2+ signaling, autophagy, lipid metabolism, ATP production, axonal transport, ER stress responses and synaptic dysfunction. ER–mitochondria signaling involves specialized regions of ER, called mitochondria-associated membranes (MAMs). Owing to their role in neurodegenerative processes, MAMs have gained attention as they appear to be associated with all the major neurodegenerative diseases. Furthermore, their specific role within neuronal maintenance is being revealed as mutant genes linked to major neurodegenerative diseases have been associated with damage to these specialized contacts. Several studies have now demonstrated that these specialized contacts regulate neuronal health and synaptic transmission, and that MAMs are damaged in patients with neurodegenerative diseases. This Review will focus on the role of MAMs and ER–mitochondria signaling within neurons and how damage of the ER–mitochondria axis leads to a disruption of vital processes causing eventual neurodegeneration.

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Section: Er-mitochondria Tethering Proteins In Neuronsmentioning

confidence: 99%

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Markovinović

Greig

Martín‐Guerrero

et al. 2022

Journal of Cell Science

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“…Ultrastructural studies have found that MERCSs are abundant in diverse tissues and cell types, which are critical for the coordination of functions of these two organelles. Indeed, it has been proposed to be involved in biochemical and signaling functions, such as lipid synthesis, Ca 2+ homeostasis, and the control of intracellular transports and mitochondrial dynamics (Rowland and Voeltz 2012;Valm et al, 2017;Aoyama-Ishiwatari and Hirabayashi 2021;Lin et al, 2021). The connection and reaction between the ER and mitochondria are greatly dependent on complementary membrane proteins and lipids, which tether the two organelles to the MERCSs.…”

Section: Mercss and Its Intracellular Functionsmentioning

confidence: 99%

Mitochondrial Dynamics, Mitophagy, and Mitochondria–Endoplasmic Reticulum Contact Sites Crosstalk Under Hypoxia

Wang

Tan

Miao

et al. 2022

Front. Cell Dev. Biol.

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Mitochondria are double membrane organelles within eukaryotic cells, which act as cellular power houses, depending on the continuous availability of oxygen. Nevertheless, under hypoxia, metabolic disorders disturb the steady-state of mitochondrial network, which leads to dysfunction of mitochondria, producing a large amount of reactive oxygen species that cause further damage to cells. Compelling evidence suggests that the dysfunction of mitochondria under hypoxia is linked to a wide spectrum of human diseases, including obstructive sleep apnea, diabetes, cancer and cardiovascular disorders. The functional dichotomy of mitochondria instructs the necessity of a quality-control mechanism to ensure a requisite number of functional mitochondria that are present to fit cell needs. Mitochondrial dynamics plays a central role in monitoring the condition of mitochondrial quality. The fission–fusion cycle is regulated to attain a dynamic equilibrium under normal conditions, however, it is disrupted under hypoxia, resulting in mitochondrial fission and selective removal of impaired mitochondria by mitophagy. Current researches suggest that the molecular machinery underlying these well-orchestrated processes are coordinated at mitochondria–endoplasmic reticulum contact sites. Here, we establish a holistic understanding of how mitochondrial dynamics and mitophagy are regulated at mitochondria–endoplasmic reticulum contact sites under hypoxia.

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“…MCSs formed between mitochondria and ER have been the most widely studied, with it being proposed that they play crucial roles in various biochemical and signaling functions such as Ca2+ homeostasis, ROS production, lipid biosynthesis, and trafficking—alongside the regulation of mitochondrial division, fusion, and mtDNA replication, autophagosome biogenesis, and autophagy [ 68 ]. These contacts are also involved in different cell dysfunctions and pathologies, including gastrointestinal inflammations, and colorectal cancer [ 69 ], traumatic brain injury [ 70 ], neurodegenerative diseases [ 71 ], metabolic diseases [ 72 ], cardiovascular diseases [ 73 ], and mood disorders [ 74 ], as well as with aging and age-related diseases [ 75 , 76 ].…”

Section: Photoreceptor-rpe Cells In Early Amdmentioning

confidence: 99%

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

Fehér¹,

Élő

István

et al. 2022

GeroScience

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Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota—mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch’s membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch’s membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)—now called postbiotics—in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

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Endoplasmic Reticulum–Mitochondria Contact Sites—Emerging Intracellular Signaling Hubs

Cited by 40 publications

References 101 publications

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Mitochondrial Dynamics, Mitophagy, and Mitochondria–Endoplasmic Reticulum Contact Sites Crosstalk Under Hypoxia

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

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