Institution: Pontifical Catholic University of PR

Email: ceidy_torres@pucpr.edu

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor neurons of the central nervous system. ALS is grouped into two types: no family history known as sporadic ALS (sALS) and linked to family inheritance know as familial ALS (fALS). The 20% of familial ALS (fALS) is associated to mutations encoding Super Oxide Dismutase 1 (SOD1) gene. Exist over 200 missenses mutations in SOD1 gene associated to ALS. The most studies mutations cause changes in amino acids sequence of Sod1 protein, such as A3V, G36R, H47Q, G92A, and S133N in humans. The Sod1 is part of a group of antioxidants enzymes defenses against to imbalance of the reactive oxygen species (ROS) production into the cell. The Sod1 converts superoxide anion to hydrogen peroxide. In previous studies have been found that the mutants Sod1 proteins lead to the formation of misfolded proteins aggregates causing mitochondrial dysfunction and, the toxic an interaction with Bcl-2, an anti-apoptotic protein in the mitochondria. Also presents inclusion bodies, aberrant axonal transport, and metabolic failures. ALS and other neurodegenerative diseases are characterized by the high production the ROS and dysfunctional mitochondria. Recent few studies have shown that the autophagy process has been implicated in ALS progression and contribute with the elimination of the aggregates of proteins and dysfunctional mitochondria. Even though, more experiments are needed to elucidate the possible interactions between SOD1 and autophagy, but no studies found related to mitophagy. Mitophagy is a type of autophagy that involves autophagosomes formation to carry damaged or dysfunctional mitochondria to fuse with lysosome/vacuole for degradation in eukaryotic cells (vacuole in yeast). The Atg32 is receptor protein expressed in the outer membrane of damage mitochondria which interact with Atg11 a protein expressed in the pre-autophagosome membrane; this interaction is the key step of mitophagy process. The main objective is study mitophagy through the activation of Atg32 and the effects of the SOD1G93A mutation under oxidative stress condition in ALS yeast model. This project will contribute to the understanding of the cellular and molecular basics that can possible exist between mutants SOD1 associated to fALS and the mitophagy mechanism.