China
Africa
Explore chapters and articles related to this topic
Insulin Signaling Modulates Neuronal Metabolism
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Qian Huang, Jialin Fu, Kelly Anne Borges, Weikang Cai
Insulin signaling up-regulates the expression of MSR genes in an ERK-dependent manner (Figure 3.3). These regulated genes include master transcriptional factors (ATF4, CHOP), along with their target proteins including mitochondrial chaperones (HSP60 and HSP10) and proteases (ClPP and LONP1). In this way, insulin potentiates mitochondrial stress response (MSR) capacity to fight for mitochondrial damage caused by various cellular stressors (128). Supporting this, MSR protein expression is decreased in the hypothalamic neurons of diet-induced obese mice, which contributes to excessive mitochondrial damage, leading to irreversible mitochondrial fission and mitophagy (129, 130). Such functional deterioration in neurons under metabolic stressors, however, can be reversed by insulin treatment. More importantly, intranasal insulin treatment improved the metabolic phenotypes of diet-induced obesity, including decreased food intake and decreased weight gain (129, 130). Together, these data strongly suggest that insulin regulates MSR network in neurons to counteract cellular stress-induced mitochondrial protein misfolding and mitochondrial dysfunction.
Introduction to lactic acidemias
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
A recent addition to mitochondrial diseases has been a syndrome associated with LONP1, which evokes mitochondrial AAA* Lon Protease [58]. Entitled CODAS syndrome, cerebral, ocular, dental, auricular, skeletal syndrome (MIM600373), the disease appears to result from alteration rather than complete absence of a complicated function of LON-dependent proteins, in which there is defective ATP-dependent proteolysis, swollen mitochondria, defective cytochrome oxidase, and impaired mitochondrial function. Patients have flattened midface, ptosis, crumpled ears, paretic vocal cords, and nuclear cataracts.
A Novel Mutation p.S93R in CRYBB1 Associated with Dominant Congenital Cataract and Microphthalmia
Published in Current Eye Research, 2020
Aixia Jin, Yu Zhang, Dongchang Xiao, Mengqing Xiang, Kangxin Jin, Mingbing Zeng
By using the whole exome sequencing to search for the causative gene(s), mutations in genes CRYBB1, PLK4, SALL2, TGM3, APRT, LONP1, GNAS, FBN1, HSPG2, etc. were found in the proband, but only CRYBB1 and TGM3 mutations were shared by all affected individuals. However, the TGM3 heterozygous mutation (c.1460T>C) was also found in the unaffected individual IV:3. The TGM3 mutations are known to be recessive mutations causing the Uncombable Hair Syndrome, and therefore TGM3 was ruled out as the causative gene. A point mutation c.279C>G in CRYBB1 gene was identified to be present in all affected individuals but not in unaffected individuals. The mutation was further verified by direct Sanger sequencing (Figure 2b). The c.279C residue is completely conserved in all human genomes, as shown in supplementary Figure S1. There is no single nucleotide polymorphism (SNP) associated with the site. The possibility of SNP was further ruled out by examinations in 1000 Genomes Project,23 the Exome Aggregation Consortium,24 the Exome Variant Server/NHLBI GO Exome Sequencing Project (ESP) (http://evs.gs.washington.edu/EVS/) and other online resources.
Misconnecting the dots: altered mitochondrial protein-protein interactions and their role in neurodegenerative disorders
Published in Expert Review of Proteomics, 2020
Mara Zilocchi, Mohamed Taha Moutaoufik, Matthew Jessulat, Sadhna Phanse, Khaled A. Aly, Mohan Babu
Mt proteins operate as part of modular, biological subsystems that are linked together by extensive networks of physical interactions. Thus, it is likely that NDs result from unfavorable rewiring of these associations. For instance, interactions of the mt fission GTPase dynamin-related protein-1 (DRP1) with the amyloid precursor protein (APP) and the phosphorylated microtubule-associated TAU protein trigger excessive mt fragmentation and synaptic deficiencies, leading to neuronal damage [12,13]. Likewise, altered human mt-matrix chaperone-protease complex, ClpXP, plays a vital role in several diseases [14], including PD [15]. Another demonstration of undesirable rewiring of protein associations is the pathological link between LONP1 protease and HSPA9 chaperone and the phenotypes of CODAS (i.e. cerebral, ocular, dental, auricular and skeletal) and EVEN-PLUS (i.e. epiphyseal, vertebral, ear, nose, plus associated findings) syndromes, essentially defining a family of ‘mt chaperonopathies’, affecting the nervous system [16,17]. Therefore, high-resolution mapping of altered mtPPI networks and their role in NDs can reveal the molecular attributes of disease, identify prospective drug targets, and inspire the development of new and more personalized therapeutics [18,19].
In vivo impact assessment of orally administered polystyrene nanoplastics: biodistribution, toxicity, and inflammatory response in mice
Published in Nanotoxicology, 2021
Yun Ju Choi, Jun Woo Park, Yong Lim, Sungbaek Seo, Dae Youn Hwang
Next, we examined the biodistribution of NP in the liver, kidney and intestine of ICR mice after 2 weeks administration of either vehicle, PurNP, or three doses of NP. Weights of the liver, kidneys and intestines, as well as the biodistribution of NP in these organs, are presented in Figure 3. The weight of all three organs remained constant, with no statistically significant difference in all mice of subset groups (Figure 3(a)). However, a significant alteration was detected in the total NP amount accumulated in each organ. The level of accumulated NP was remarkably and dose-dependently increased in each tissue, although levels in the PurNP group (liver, 0.62 ± 1.21; kidney, 2.74 ± 2.95; intestine, 4.29 ± 1.79) were similar to the LoNP group (liver, 0.45 ± 0.12; kidney, 2.15 ± 0.93; intestine, 4.28 ± 1.79). Especially, in all treated groups, the total NP accumulated in the intestine (PurNP, 4.29 ± 1.79; LowNP, 4.28 ± 1.79; MidNP, 14.06 ± 2.05; HigNP, 29.71 ± 2.16) was significantly higher than levels obtained in the liver (PurNP, 0.62 ± 1.21; LowNP, 0.45 ± 0.12; MidNP, 1.77 ± 3.57; HigNP, 4.35 ± 2.49) and kidney (PurNP, 2.74 ± 2.95; LowNP, 2.15 ± 0.93; MidNP, 9.99 ± 2.18; HigNP, 15.89 ± 6.96) (Figure 3(b)). We further calculated the amount of NP accumulated per gram of each tissue (µg/g), based on the biodistribution of NP in the liver, kidney and intestine of mice exposed to NP. Alteration patterns of these levels were very similar to the total NP accumulated in each tissue (Figure 3(c)). In particular, PurNP showed lower accumulated NP levels (liver, 0.62 ± 1.21; kidney, 2.74 ± 2.95) than the HigNP group (liver, 4.35 ± 2.49; kidney, 15.89 ± 6.96). Moreover, we calculated the fraction of the total administered NP according to the investigated tissue (amount of NP distributed in tissue per amount of the total administration). The fractions of distribution obtained in the liver, kidney, and intestine were 0.64 ± 0.17%, 3.01 ± 1.33%, and 6.11 ± 2.55%, respectively, in the LowNP group; 0.51 ± 1.02%, 2.85 ± 0.62%, and 4.02 ± 0.59%, respectively, in the MidNP group; and 0.62 ± 0.35%, 2.27 ± 0.99%, and 4.24 ± 0.31%, respectively, in the HigNP group. These results indicate that oral administration of NP for 2 weeks results in high accumulation of NP in the intestine (4–6%) and kidney (2–3%) of the ICR mice. Moreover, we postulate that the PurNP solution has a lower concentration of NP due to the efficient removal from HigNP by the coagulation-based plastic removal method.