A correlation between redox imbalance and altered mitochondrial quality control pathway in Autistic Spectrum Disorder

Full Title: A correlation between redox imbalance and altered mitochondrial quality control pathway in Autistic Spectrum Disorder

Journal: Free Radical Biology and Medicine

Year of Publication: 2017

PHHI Author(s): Giuseppe Valacchi
Publication Author(s): Francesca Ferrara, Alessandra Pecorelli, Franco Cervellati, Mascia Benedusi, Arianna Romani, Carlo Cervellati, Joussef Hayek, Giuseppe Valacchi

Abstract:

The Autistic Spectrum Disorder (ASD) refers to a range of conditions classified as neurodevelopmental disorders characteristic of the early childhood.

Over the last 50 years, considerable efforts have been made to understand pathogenesis of ASD: it is generally accepted that a lot of causes could trigger the disease.

Since growing evidences described an association between oxidative stress and mitochondrial dysfunction in ASD, we investigated the possible defects of mitochondrial quality control pathway as contributing factors to the altered redox homeostasis.

Using freshly skin fibroblasts isolated from ASD patients and healthy subjects, we demonstrated in autistic cells an increased levels of 4HNE protein adducts – a major secondary product of lipid peroxidation – and catalase, one of the main enzymes of the cellular defensive system.

Transmission electron microscope (TEM) analysis demonstrated an altered mitochondrial morphology in autistic fibroblasts. An increased expression of the genes that encode for molecules involved in mitochondrial fission/fusion processes, was also detected. In addition, overregulation of PINK1, but decreased Parkin expression, both associated to mitophagyprocess, were observed.

Taken together our findings provide new insights on the possible contribution of the altered mitochondrial quality control pathway in the redox imbalance of ASD patients.

Link to Article: https://www.sciencedirect.com/science/article/pii/S0891584917304264