Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3.

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation

Relação entre os níveis de vitamina A e os marcadores bioquímicos do estado nutricional de ferro em crianças e adolescentes Relationship between vitamin A and biochemical markers of iron status in children and adolescents

OBJETIVO: Verificar a relação entre vitamina A e os marcadores bioquímicos da situação nutricional do ferro. MÉTODOS: Participaram deste estudo 178 indivíduos com idade entre 7 e 17 anos, residentes na cidade de Jequié (BA). Os indivíduos foram submetidos a exame de sangue para dosagem de retinol e de marcadores bioquímicos do estado nutricional relativo ao ferro. Além disso, foram realizados exames antropométricos, parasitológico de fezes e coletadas informações de consumo dietético de ferro e das condições sócio-ambiental e domiciliar da família. Utilizou-se a análise de regressão linear múltipla como técnica estatística para avaliar a associação de interesse. RESULTADOS: Constatou-se associação positiva e estatisticamente significante entre os níveis de retinol sérico e a concentração de hemoglobina (p=0,007), ferro sérico (p=0,010) e transferrina saturada (p=0,027). Esses efeitos se mantiveram após ajuste dos modelos pelas variáveis demográficas, infecções parasitárias (Schistosoma mansoni, Trichiura trichuris, Ascaris lumbricoides e ancilostomídeos), consumo de ferro alimentar biodisponível e condições ambientais e domiciliares. CONCLUSÃO: A vitamina A parece contribuir para elevar o ferro orgânico da população, em especial, em áreas onde a deficiência de vitamina A e a anemia coexistem.<br>OBJECTIVE: The objective of this study was to verify the relationship between vitamin A and the biochemical markers of iron status. METHODS: A total of 178 individuals aging from 7 to 17 years participated in this study, all living in Jequié, BA. The individuals were submitted to blood tests to dose retinol and biochemical iron markers. Furthermore, anthropometric measurements and stool analyses were done and dietary information regarding iron intake, socio-environmental and home conditions of the family were collected. Multiple linear regression analysis was done to assess the association of interest. RESULTS: A positive and statistically significant association was found between the levels of serum retinol and hemoglobin (p=0.007), serum iron (p=0.010) and iron-saturated tranferrin (p=0.027). These findings remained unchanged after adjusting the models for demographic variables, parasitic infections (Schistosoma mansoni, Trichiura trichuris, Ascaris lumbricoides and ancylostomiasis), consumption of bioavailable dietary iron and environmental and home conditions. CONCLUSION: Vitamin A seems to contribute to the increase of organic iron of the population, especially in areas were deficiency of vitamin A and iron-deficiency anemia coexist