The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

Chang, Yi‐Cheng; Hee, Siow‐Wey; Hsieh, Meng-Lun; Jeng, Yung‐Ming; Chuang, Lee‐Ming

doi:10.1155/2015/972891

Cited by 15 publications

(14 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, it has recently been shown that autophagy negatively regulates inflammasome activation (reviewed in Pedraza‐Alva, Perez‐Martinez, Valdez‐Hernandez, Meza‐Sosa, & Ando‐Kuri, ), supporting previous observations indicating an inverse correlation between autophagy and inflammation in different pathological settings, affecting peripheral organs (Bianco, Girardelli, & Tommasini, ; Chang, Hee, Hsieh, Jeng, & Chuang, ; Lapaquette, Guzzo, Bretillon, & Bringer, ). Although, François et al, () reported that in the APPswe/PS1dE9 transgenic mice, inflammation could induce autophagy in older mice (François et al, ), the relationship between inflammation and autophagy on AD development remains largely unclear.…”

Section: Discussionsupporting

confidence: 67%

Autophagy impairment by caspase‐1‐dependent inflammation mediates memory loss in response to β‐Amyloid peptide accumulation

Álvarez-Arellano

Pedraza-Escalona

Ayala

et al. 2017

J of Neuroscience Research

View full text Add to dashboard Cite

β-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by β-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, β-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death. Thus, here we evaluated whether the inflammatory response induced by the β-Amyloid peptides impairs memory via disrupting the autophagic flux. We show that male mice overexpressing β-Amyloid peptides (5XFAD) but lacking caspase-1, presented reduced β-Amyloid plaques in the cortex and in the hippocampus; restored brain autophagic flux and improved learning and memory capacity. At the molecular level, inhibition of the inflammatory response in the 5XFAD mice restored LC3-II levels and prevented the accumulation of oligomeric p62 and ubiquitylated proteins. Furthermore, caspase-1 deficiency reinstates activation of the AMPK/Raptor pathway while down-regulating AKT/mTOR pathway. Consistent with this, we found an inverse correlation between the increase of autophagolysosomes in the cortex of 5XFAD mice lacking caspase-1 and the presence of mitochondria with altered morphology. Together our results indicate that β-Amyloid peptide-induced caspase-1 activation, disrupts autophagy in the cortex and in the hippocampus resulting in neurodegeneration and memory loss.

show abstract

Section: Discussionsupporting

confidence: 67%

Autophagy impairment by caspase‐1‐dependent inflammation mediates memory loss in response to β‐Amyloid peptide accumulation

Álvarez-Arellano

Pedraza-Escalona

Ayala

et al. 2017

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…Therefore, a precise integration of both metabolic and inflammatory pathways is essential for the adaptations of hepatic metabolism to environment, but more generally for the regulation of whole-body metabolism. In agreement, mitochondrial dysfunction and ER stress have been largely and independently associated with metabolic diseases, such as obesity, type 2 diabetes mellitus (T2DM) (Chang et al 2015, Rieusset 2015, Salvado et al 2015, Hasnain et al 2016) and non-alcoholic fatty liver diseases (NAFLD) (Begriche et al 2013, Takaki et al 2014, Ashraf & Sheikh 2015. Moreover, the strong interplay between the two organelles and immune signaling (Hummasti & Hotamisligil 2010, Chaudhari et al 2014 further highlights their involvement in the progression toward metabolic diseases.…”

Section: Introductionmentioning

confidence: 89%

Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases

Tubbs

Rieusset

2017

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Beyond the maintenance of cellular homeostasis and the determination of cell fate, ERmitochondria contact sites, defined as mitochondria-associated membranes (MAM), start to emerge as an important signaling hub that integrates nutrient and hormonal stimuli and adapts cellular metabolism. Here, we summarize the established structural and functional features of MAM and mainly focus on the latest breakthroughs highlighting a crucial role of organelle crosstalk in the control of metabolic homeostasis. Lastly, we discuss recent studies that have revealed the importance of MAM in not only metabolic diseases but also in other pathologies with disrupted metabolism, shedding light on potential common molecular mechanisms and leading hopefully to novel treatment strategies.

show abstract

“…However, autophagy activity is greatly up-regulated in response to nutrient limitation or to an altered intracellular milieu. A dysregulation of autophagy activity contributes to the pathology of multiple diseases (Chang et al 2015;Tai et al 2016;Edens et al 2016), including complications of pregnancy (Hung et al 2012;Kanninen at el. 2013b;Gao et al 2015;Brickle et al 2015;Agrawal et al 2015).…”

mentioning

confidence: 99%

The influence of oxidative stress and autophagy cross regulation on pregnancy outcome

Ramos

2016

Cell Stress and Chaperones

View full text Add to dashboard Cite

The generation of reactive oxygen species (ROS), a byproduct of aerobic energy metabolism, is maintained at physiological levels by the activity of antioxidant components. Insufficiently opposed ROS results in oxidative stress characterized by altered mitochondrial function, decreased protein activity, damage to nucleic acids, and induction of apoptosis. Elevated levels of inadequately opposed ROS induce autophagy, a major intracellular pathway that sequesters and removes damaged macromolecules and organelles. In early pregnancy, autophagy induction preserves trophoblast function in the low oxygen and nutrient placental environment. Inadequate regulation of the ROS-autophagy axis leads to abnormal autophagy activity and contributes to the development of preeclampsia and intrauterine growth restriction. ROS-autophagy interactions are altered at the end of gestation and participate in the initiation of parturition at term. The induction of high levels of ROS coupled with a failure to induce a corresponding increase in autophagy results in the triggering of preterm labor and delivery.Keywords Oxidative stress . Autophagy . Preeclampsia . Intrauterine growth restriction . Preterm birth . PregnancyReactive oxygen species (ROS), such as superoxide radicals, hydroxyl radicals, alkoxy radicals as well as the non-radical intermediates hydrogen peroxide, ozone, and singlet oxygen, are byproducts of aerobic energy metabolism (Sies 1991;Finkel 2011). The concentration of these radicals is maintained at physiological levels by activity of the antioxidant enzymes superoxide dismutase, catalase, and peroxiredoxins as well as by concentrations of glutathione and vitamins C and E. When this system becomes out of balance, the generation of insufficiently opposed ROS results in altered mitochondrial function, a diminution of protein activity, damage to nucleic acids, and induction of apoptosis. The consequent tissue damage is manifested in a range of pathologies to different organ systems (Domingueti et al. 2015;Aluganti et al. 2016;Hernández et al. 2016). Recently, insufficiently regulated ROS has been recognized as a major contributor to disorders of pregnancy (Coppe et al. 2010;Redman and Sargent 2010;Menon 2014; Wu et al. 2015a, b;Zhang et al. 2015).A major pathway for removing macromolecules and organelles that have been damaged by ROS is macroautophagy, hereafter referred to as autophagy. This catabolic process is responsible for eliminating altered proteins, mitochondria, and inflammasomes from the cytoplasm. Macromolecules and organelles marked for destruction are enclosed within a doublemembrane structure called autophagosome. Its subsequent fusion with a lysosome results in degradation of the enclosed entity and release of the component amino acids, carbohydrates, nucleic acid degradation products, and lipids into the cytoplasm as building blocks for synthesis of new macromolecules or for the generation of energy by mitochondria. Autophagy is a constitutive process and functions at a low level under physiologica...

show abstract

The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

Cited by 15 publications

References 135 publications

Autophagy impairment by caspase‐1‐dependent inflammation mediates memory loss in response to β‐Amyloid peptide accumulation

Autophagy impairment by caspase‐1‐dependent inflammation mediates memory loss in response to β‐Amyloid peptide accumulation

Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases

The influence of oxidative stress and autophagy cross regulation on pregnancy outcome

Contact Info

Product

Resources

About