Selective Loss of the Iron-Sulfur Subunit of the Succinate Dehydrogenase Enzyme Complex in Alzheimer's Brains: Implications for Mitochondrial Function and Disease Pathogenesis
Abstract
Mitochondria are vital for energy production in neurons. Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer's disease (AD). Neurons primarily rely on glucose as their energy source, which is metabolized through glycolysis and further processed in the mitochondria via Krebs cycle and oxidative phosphorylation (OXPHOS). Succinate dehydrogenase (SDH), an enzyme complex involved in both Krebs cycle and OXPHOS, plays a significant role. SDH comprises soluble and membrane-spanning subunits. The former consists of a flavoprotein (SDHA) and an iron-sulfur protein (SDHB) catalyzing the conversion of succinate to fumarate in the matrix. This reaction is coupled to the conversion of quinol to quinone during OXPHOS by the membrane-spanning subunits (SDHC and SDHD). SDH dysfunction disrupts mitochondrial activity, impairing energy production and cellular metabolism. In AD brains, reduced levels and activity of SDH have been observed, however, the role of specific subunits is not known. Therefore, this retrospective study aims to investigate whether all or specific SDH subunits are affected during the pathogenesis of AD in human brains. This research study's purpose is to unravel the role of Succinate Dehydrogenase (SDH) subunits in the context of Alzheimer's disease (AD). Hence, the retrospective investigation aims to discern whether all or specific SDH subunits are affected during the progression of AD in human brains. Essentially, the goal of this is to pinpoint the precise role of these subunits and focusing on understanding the implications of their dysfunction in AD-related mitochondrial disruption. Providing critical insights into the disease's pathogenesis and potential avenues for targeted therapeutic interventions.
Faculty Sponsors
Dr. Mohammad Golam Sabbir
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Selective Loss of the Iron-Sulfur Subunit of the Succinate Dehydrogenase Enzyme Complex in Alzheimer's Brains: Implications for Mitochondrial Function and Disease Pathogenesis
Alvin Sherman Library
Mitochondria are vital for energy production in neurons. Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer's disease (AD). Neurons primarily rely on glucose as their energy source, which is metabolized through glycolysis and further processed in the mitochondria via Krebs cycle and oxidative phosphorylation (OXPHOS). Succinate dehydrogenase (SDH), an enzyme complex involved in both Krebs cycle and OXPHOS, plays a significant role. SDH comprises soluble and membrane-spanning subunits. The former consists of a flavoprotein (SDHA) and an iron-sulfur protein (SDHB) catalyzing the conversion of succinate to fumarate in the matrix. This reaction is coupled to the conversion of quinol to quinone during OXPHOS by the membrane-spanning subunits (SDHC and SDHD). SDH dysfunction disrupts mitochondrial activity, impairing energy production and cellular metabolism. In AD brains, reduced levels and activity of SDH have been observed, however, the role of specific subunits is not known. Therefore, this retrospective study aims to investigate whether all or specific SDH subunits are affected during the pathogenesis of AD in human brains. This research study's purpose is to unravel the role of Succinate Dehydrogenase (SDH) subunits in the context of Alzheimer's disease (AD). Hence, the retrospective investigation aims to discern whether all or specific SDH subunits are affected during the progression of AD in human brains. Essentially, the goal of this is to pinpoint the precise role of these subunits and focusing on understanding the implications of their dysfunction in AD-related mitochondrial disruption. Providing critical insights into the disease's pathogenesis and potential avenues for targeted therapeutic interventions.
