Anti-Oxidant Defense System and Lipid Peroxidation

What is the function of the Anti-Oxidant Defense System (AODS)

It manages and mitigates the risk of oxidative stress and free radical damage to cellular structures

Which cellular molecules are major targets for free radical attack

Polyunsaturated fatty acids (PUFAs) in lipid bilayers

How does lipid peroxidation begin in polyunsaturated fatty acids

By hydrogen atom abstraction from the hydrocarbon chain initiating a free radical chain reaction

Why are PUFAs particularly vulnerable to oxidative damage

Due to their multiple double bonds which make hydrogen abstraction easier and radicals more stable

What types of cellular damage can oxidative stress cause

Damage to lipids

What role do enzymes in the AODS play

They neutralize free radicals and terminate chain reactions before extensive damage occurs

What enzyme converts superoxide radicals into hydrogen peroxide and oxygen

Superoxide dismutase (SOD)

Where is manganese-dependent superoxide dismutase located

In the mitochondrial matrix

What is the role of catalase in oxidative defense

Catalase converts hydrogen peroxide into water and oxygen to reduce oxidative damage

What molecule acts as a reducing agent to detoxify peroxides in cells

Glutathione

Which enzyme uses glutathione to neutralize hydrogen peroxide

Glutathione peroxidase

How do lipid radicals propagate the chain reaction in membranes

Lipid radicals react with oxygen to form peroxyl radicals which attack adjacent lipids

What is the end product of lipid peroxidation that can crosslink proteins and DNA

Malondialdehyde (MDA)

How does oxidative damage to membrane lipids affect cell function

It compromises membrane fluidity and permeability leading to cell dysfunction or death

What non-enzymatic antioxidants also protect against lipid peroxidation

Vitamin E (tocopherol) and Vitamin C (ascorbate)

How does vitamin E protect lipids from peroxidation

It donates electrons to lipid radicals stopping the propagation of free radical damage

What is the relationship between oxidative stress and chronic diseases

Excess oxidative stress and lipid peroxidation contribute to aging

How does the cell regenerate oxidized vitamin E

Vitamin C regenerates vitamin E by reducing the tocopheroxyl radical back to its active form

What is the primary source of reactive oxygen species (ROS) in cells

The mitochondrial electron transport chain (ETC)

Which complexes of the ETC are most associated with ROS production

Complex I and Complex III

How are superoxide radicals generated during mitochondrial respiration

By leakage of electrons to oxygen at ETC complexes forming O2− (superoxide)

Why is superoxide considered harmful to cells

Because it initiates free radical chain reactions that damage lipids

What enzyme converts superoxide into less reactive species

Superoxide dismutase (SOD)

What reactive oxygen species is formed when superoxide reacts with nitric oxide

Peroxynitrite (ONOO−)

What conditions increase mitochondrial ROS production

High membrane potential

How does mitochondrial ROS contribute to cellular signaling

ROS act as signaling molecules regulating processes like apoptosis and hypoxic responses

What antioxidant molecules and enzymes are found in mitochondria

Superoxide dismutase (MnSOD)

How does mitochondrial dysfunction exacerbate ROS generation

Impaired ETC function causes more electron leakage and ROS formation

What role does uncoupling proteins (UCPs) have in ROS regulation

UCPs reduce mitochondrial membrane potential and limit ROS production by mild uncoupling

How can excessive ROS lead to apoptosis

By damaging mitochondrial membranes

What is the difference between physiological and pathological ROS levels

Physiological ROS regulate signaling; pathological ROS cause oxidative damage and cell death

What is the primary mitochondrial antioxidant enzyme that converts superoxide to hydrogen peroxide

Manganese superoxide dismutase (MnSOD)

How is hydrogen peroxide detoxified in mitochondria

By glutathione peroxidase and catalase enzymes

What is the role of glutathione in mitochondrial antioxidant defense

It acts as a reducing agent to neutralize ROS and regenerate other antioxidants

How is glutathione maintained in its reduced form

By the enzyme glutathione reductase using NADPH as an electron donor

What is the consequence of impaired antioxidant defense in mitochondria

Accumulation of ROS leading to oxidative damage to mitochondrial DNA

How does oxidative damage to mitochondrial DNA affect cellular function

It can impair mitochondrial gene expression and ETC function

Name diseases commonly associated with mitochondrial oxidative stress

Parkinson’s disease

How do ROS contribute to the pathogenesis of neurodegenerative diseases

By causing neuronal damage through lipid peroxidation

What is the role of mitochondrial ROS in ischemia-reperfusion injury

Excess ROS generated on reperfusion damage cells and trigger inflammation and cell death

How can antioxidant therapies target mitochondrial oxidative stress

By scavenging ROS

What are the limitations of current antioxidant therapies for mitochondrial diseases

Poor mitochondrial targeting

How does mitochondrial biogenesis influence oxidative stress

Increased mitochondrial biogenesis can dilute damaged mitochondria and improve cellular redox balance

What role does mitophagy play in managing oxidative damage

It selectively degrades damaged mitochondria to prevent excess ROS accumulation

What is oxidative phosphorylation

The process of ATP production in mitochondria driven by electron transport and proton gradient

Which protein complex synthesizes ATP using the proton gradient

ATP synthase (Complex V)

What is the source of the proton gradient used in oxidative phosphorylation

The electron transport chain pumps protons from the mitochondrial matrix to the intermembrane space

Which complexes of the ETC pump protons across the inner mitochondrial membrane

Complexes I

What molecule is the final electron acceptor in the ETC

Molecular oxygen (O2)

What is the chemiosmotic hypothesis

The theory that ATP synthesis is powered by the flow of protons down their electrochemical gradient through ATP synthase

How many protons approximately drive the synthesis of one ATP molecule

About 3 protons per ATP

What is mitochondrial fusion

The process of joining two mitochondria to form a larger interconnected network

What proteins mediate mitochondrial fusion

Mitofusins (Mfn1

What is mitochondrial fission

The division of a mitochondrion into two smaller organelles

Which protein is key for mitochondrial fission

Dynamin-related protein 1 (Drp1)

How does mitochondrial dynamics affect cellular health

It regulates mitochondrial quality control

What happens when mitochondrial fission is excessive

Leads to fragmented mitochondria

How does mitochondrial fusion support cellular function

By mixing mitochondrial contents

What role does oxidative phosphorylation efficiency play in ROS production

Inefficient electron transfer increases electron leakage and ROS generation

How can defects in oxidative phosphorylation contribute to disease

Cause mitochondrial diseases