Abstract 2264 A Complex I deficiency induces iron misregulation to promote neurodegeneration
Year: 2024
Type: conference-abstract
Abstract: Iron is a vital element in the human body that plays a pervasive role in many biological processes including the electron transport chain (ETC) in mitochondria.Despite its critical importance, excess iron is toxic to the body, which is considered pathogenic in many diseases such as Parkinson's disease (PD).In PD the first complex of the ETC (Complex I) is deactivated and iron deposition is similarly observed.We hypothesize, the Complex (I) deficiencies, which normally contains 8 Fe-S clusters, induces misregulation of Fe-S cluster biogenesis and iron misregulation.To test this, we are using dopaminergic-differentiated SH-SY5Y neurons with chemical inhibitors of Complex I and genetic knockout of Complex (I) to study effects of iron misregulation on inducing reactive oxygen species generation, redox imbalances and oxidative stress damage thus leading to cell death.We observed decreases in expression of iron-sensitive proteins (TFR1 &DMT1) by qPCR and W.B in dopaminergic-differentiated SH-SY5Y neurons treated with Complex I inhibitors.Depending on our results we can conclude that inhibition of complex I can be a direct cause of iron accumulation in PD cell line model.Uncovering the role of Complex (I) in inducing iron dyshomeostasis represents a first step in elucidating the molecular sequence of events associated in PD pathophysiology and will enable the rational pursuit of effective pharmaceutical interventions to prevent suffering of millions of people living PD or similar movement disorders.
Source: Journal of Biological Chemistry
Authors: Alaa Hassan, Anthony Grillo
Institution: University of Cincinnati
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
OpenAlex ID: W4393143420