The Effects of Increased Net Reactive Oxygen Species on Mitophagy
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Transcript of The Effects of Increased Net Reactive Oxygen Species on Mitophagy
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The Effects of Increased Net Reactive Oxygen Species on MitophagyDONALD TA
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Dementia Lin et al (2006) says that oxidative stress has been thought to contribute to aging, which is a major risk factor for dementia (But how?)
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What does ethanol do to a cell? Increases oxidative stress How?◦Increases cellular metabolism◦Lowers levels of antioxidants
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Increased oxidative stress
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Reddy et al (2013) found that alcohol-induced oxidative stress can alter the brain mitochondrial make-up and this is due to accumulation of dysfunctional mitochondria
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Mitophagy Selective breakdown of dysfunctional or damaged mitochondria Mitochondria gets tagged for degradation degraded in lysosome/vacuole Prevents accumulation of the damaged or dysfunctional mitochondria
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Mitophagy is not perfect Environmental factors (Such as abundance of ethanol exposure) Process can get overwhelmed
◦ Imbalance of Reactive Oxygen Species in Cell (ROS)◦ Not an even ratio of ROS being produced and removed
accumulation of damaged or dysfunctional mitochondria Net ROS
◦ Main contributor to aging
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What do I want to know?I hypothesize that increased ethanol exposure will elicit lower levels of GFP processing
Om45-green fluorescence protein is a mitochondrial outer membrane protein complex that binds to the mitochondria
Mitophagy initiatedmitochondria degraded in lysosome/vacuoleOm45 degraded, but GFP in-tact
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Does ethanol elicit Om45-GFP processing in yeast cells? Produce yeast cells expressing Om45-GFP
Expose yeast cell groups to different levels of ethanol
Measure the levels of GFP still in-tact◦How will I measure these levels?
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Western Blot Used to detect for specific proteins in given sample
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Problems? Mechanism of mitophagy is still poorly understood
Ethanol exposure can produce factors other than increased ROS
Critical points of ethanol varies by organism
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Overall Picture Ethanol increases oxidative stress in cell can overwhelm mitophagy mechanism
Decrease in levels of mitophagy in a cell which can cause an accumulation of dysfunctional/damaged mitochondria
I will measure this by determining if ethanol elicits GFP processing in yeast cells
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Why should you care? These accumulations of dysfunctional/damaged mitochondria have been liked to aging and neurodegenerative diseases such as dementia
1 in 7 people develop dementia when they reach 70 years old according to the National Institute of Health in 2007
If my hypothesis is correct, that ethanol will NOT elicit GFP processing◦ Alcohol and dementia◦ Science Community