Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans

Tubbs, Emily; Chanon, Stéphanie; Robert, M.; Bendridi, Nadia; Bidaux, Gabriel; Chauvin, Marie-Agnès; Ji-Cao, Jingwei; Durand, Christine; Gauvrit-Ramette, Daphné; Vidal, Hubert; Lefai, Étienne; Rieusset, Jennifer

doi:10.2337/db17-0316

Cited by 164 publications

(193 citation statements)

References 46 publications

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“…Mfn2 or Grp75 overexpression reversed the effects of palmitate on MAM proteins and on insulin signaling . Moreover, myotubes from obese patients and from obese patients with type 2 diabetes showed decreased mitochondria–ER contacts compared to those of healthy patients . In contrast to these results, Arruda et al found an increase in the MAM proteins MCU and RyR in soleus muscles from ob/ob and HFD‐fed mice, suggesting an enrichment in MAMs under these conditions.…”

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 93%

“…Ablation of GRP75 , the bridge between IP3R and VDAC, has been reported to cause a r eduction in VDAC1/IP3R1 interactions in human liver cells and in myotubes . Moreover, GRP75 deficiency reduces insulin signaling and insulin action in HuH7 liver cells (Fig A). The depletion of GRP75 in medullary thyroid carcinoma cells induces the MEK/ERK pathway and increases oxidative stress .…”

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 94%

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Metabolic implications of organelle–mitochondria communication

2019

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Cellular organelles are not static but show dynamism—a property that is likely relevant for their function. In addition, they interact with other organelles in a highly dynamic manner. In this review, we analyze the proteins involved in the interaction between mitochondria and other cellular organelles, especially the endoplasmic reticulum, lipid droplets, and lysosomes. Recent results indicate that, on one hand, metabolic alterations perturb the interaction between mitochondria and other organelles, and, on the other hand, that deficiency in proteins involved in the tethering between mitochondria and the ER or in specific functions of the interaction leads to metabolic alterations in a variety of tissues. The interaction between organelles is an emerging field that will permit to identify key proteins, to delineate novel modulation pathways, and to elucidate their implications in human disease.

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Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 93%

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 94%

Metabolic implications of organelle–mitochondria communication

2019

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“…For example, in liver, obesity leads to a marked enhancement of MAM that alters interorganellar calcium dynamics and causes increased oxidative stress and metabolic derangement [14]. MAM disruption and miscommunication have also been implicated in muscle insulin resistance in mice and humans [15], and hepatic insulin resistance [16], respectively. Intriguingly, MAM is thought to be the site of isolation membrane for the formation of selective autophagosomes for mitochondria [17].…”

Section: Er Interconnections With Other Organellesmentioning

confidence: 99%

“…Skeletal muscle is the primary site of insulin-mediated glucose uptake and is the main organ affected by insulin resistance and diabetes. Palmitate disrupts normal insulin signaling and alters insulin sensitivity in skeletal muscle and MAM disorganization has been involved in the mechanism [15]. However, concomitant exposure to oleate abolishes ER stress in human myotubes [89].…”

Section: Insulin Receptor Modulationmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Metabolic Disorders

Ghemrawi

Battaglia-Hsu

Arnold

2018

Preprint

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Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these maladies has different physiological and clinical symptoms, they appear to share certain pathological traits such as intracellular stress and inflammation induced by metabolic derangements stemmed from over nutrition frequently aggravated by modern sedentary life style. These modern ways of living inundate cells and organs with saturating levels of sugar and fat, leading to glycotoxicity and lipotoxicity that induce intracellular stress signaling ranging from oxidative to ER stress response to cope with the metabolic insults [1]. In this review, we discuss the roles played by cellular stress and its responses in shaping metabolic disorders. We have summarized here current mechanistic insights explaining the pathogenesis of these disorders. These are followed by a discussion of the latest therapies targeting the stress response pathways.

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“…40 Abnormal MAM functions also are known to cause type 2 diabetes. 48,49 This evidence suggests that MAMs are likely a key signaling hub. Although no direct associations between kidney disease and MAMs have been reported to date, considering their function, malfunctioning MAMs potentially could cause kidney diseases.…”

mentioning

confidence: 97%

Organelle crosstalk in the kidney

Inoue

Maekawa

Inagi

2019

Kidney International

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Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. The UPR pathway in the ER also regulates mitochondrial metabolic status, indicating the pathophysiological significance of organelle crosstalk between the ER and mitochondria via the UPR pathway. In recent years, it has become obvious that communication among organelles also is conducted through direct interactions at membrane contact sites (MCSs). Organelles exchange materials including lipids, ions, and proteins at the MCS. Accordingly, alterations to these networks, such as impaired ER-mitochondria MCSs, have been linked to several diseases such as neurodegeneration and diabetes. In this review, we describe the roles of organelles in kidney diseases and the mechanisms underlying organelle communication at the MCS, and especially at the mitochondria-associated ER membrane. Potential treatment options that are focused on organelle crosstalk are discussed, in addition to the relationship between this phenomenon and various diseases, especially kidney diseases.

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Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans

Cited by 164 publications

References 46 publications

Metabolic implications of organelle–mitochondria communication

Metabolic implications of organelle–mitochondria communication

Endoplasmic Reticulum Stress in Metabolic Disorders

Organelle crosstalk in the kidney

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