Mitochondrial defect associated mutation in the DNM1L protein: a review of variants and etiologic analyzes from a database

Abstract

Mitochondria is an essential organelle in vital roles in maintaining survival, viability, cell integrity and cellular functionality. Dynamin 1 as (DNM1L) belongs to a protein family, also known as protein 1 coding dynamin family (DRP1) or dynamin protein 1 (DLP1) which is mainly in the cytosol of the cell and participates in recruitment to the outer mitochondrial membrane by anchored receptor membrane protein, involving mitochondrial fission factor (MFF), mitochondrial fission protein 1 (FIS1) and mitochondrial dynamics proteins (MID49 and MID51), this protein is involved in endocytosis mediated by the endocytic vesicle and in the balance of fusion and fission, which implies mechanisms associated with peroxisomes. In GTPases hydrolysis, DNM1L undergoes changes that induce membrane constriction and subsequently lead to membrane vesicle fission. The fusion process is primarily responsible for the fusion between the organelles in response to the formation of fusion complexes coordinated by the proteins Mifusins 1 and 2 or MFN1 and MFN2 on the outside of the cell and OPA1 on the inside. The Dynamin family are proteins regulating activity in synaptic neurons, maintaining function in organelles, when affected during cellular homeostasis is associated with the development of mitochondrial diseases linked to changes in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA).DNM1L mutation is an example of this, its defect can cause abnormal fission or fusion in the endocytic vesicle affecting mainly neuronal synaptic function leading to the development of lethal encephalopathy in children or other neurodegenerative diseases. Currently there are tools used to perform the diagnosis which make it possible to quickly and accurately identify the mtDNA mutations associated with the expression of DNM1L are used resources that identify this type of mutation through diagnostic techniques genetic and image analysis through immunofluorescence, laser scanning confocal microscopy, cell culture, micro-oximetry and Whole Exome Sequencing (WES) allowing evaluation of the genome and possible cellular changes, as well as to verify its function, spectrumassociated with DNM1L variants. In this study it was developed through a bioinformatics platform as the main tool to search for variants in the Uniprot database using the The analysis of the results obtained through the DNM1L gene as a parameter was performed to analyze the importance of the interaction of this protein in the regular maintenance of cellular health and its implications for mitochondrial diseases in the research of rare diseases. The etiology is still uncertain and has great genetic variability in several parts of the world, however scientific results were not obtained in Brazil.