Ex2 L8 - Mitochondrial Dysfunction in Aging Flashcards

1
Q

The mitochondria is…

A

the major site of cell energy metabolism (ATP synthesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

ATP is ——- and it provides energy because…

A

adenosine triphosphate, energy is stored in phosphate bonds, which break to release the energy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

ATP is used to do —— in cells such as:

A

work, such as:
- active transport
- contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

ATP is made in:

A

mitochondria (oxidative phosphorylation)
and cytoplasm (glycolysis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the important points about glycolysis?

A
  • does not consume O2 (therefore is not a source of reactive oxygen species
  • does not produce CO2
  • produces ATP rapidly but inefficiently (2 ATP per glucose)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the important points about oxidative (aerobic) ATP production?

A
  • consumes O2
  • produces CO2
  • produces ATP efficiently but slowly (each pyruvate from glucose makes over 30 ATP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

——— from ——– can undergo oxidative/aerobic ATP production.

A

glucose, fatty acids, and amino acids
from carbohydrates, lipids, and proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Oxidative/aerobic ATP production involves both —— and ——-.

A

the citric acid cycle (TCA)
the electron transport chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Reactive oxygen species are produced during…

A

Normal O2 metabolism - oxidation-reduction reactions in the ETC produce reactive oxygen species as a normal byproduct
OR
Exposure to pollutants, tobacco, radiation, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In the past it was believed that reactive oxygen species were…

A

the direct cause of aging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Small amount of reactive oxygen species are…

A

normal/expected and needed for certain functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do reactive oxygen species relate to aging?

A
  • as age increases, the amount produced increases and ability to neutralize them decreases
  • they accumulate, causing oxidative stress
  • oxidative stress causes tissue injury and inflammation that leads to aging and age-related disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the three main types of reactive oxygen species?

A

superoxide, hydrogen peroxide, and hydroxyl radicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does superoxide mutase do?

A

turn superoxide into hydrogen peroxide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does peroxidase do?

A

turns hydrogen peroxide into water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

An imbalance of —— and —— lead to ———

A

imbalance of free radicals (ROS) and antioxidants leads to oxidative stress

17
Q

Antioxidants function by ——-, not by ———

A

by neutralizing ROS, not by preventing ROS formation

18
Q

What is inflammaging?

A

increased activation of the immune system with age (mitochondria play a role)

19
Q

Although inflammaging increases activation of the immune system, it is still bad becuase:

A

the activation is dysregulated and therefore not active at the appropriate times
chronic inflammation leads to chronic activation of the signaling pathways

20
Q

How do cytokines relate to successful aging?

A

circulating levels of inflammatory cytokines are inversely correlated with successful aging because chronic inflammation leads to chronic activation of signaling pathways

21
Q

5 things caused by inflammaging are:

A
  • DNA damage
  • proinflammatory cytokines
  • oxidative stress
  • immunosenescence
  • autophagy
22
Q

What is immunosenescence?

A

immune system slows down and stops functioning

23
Q

What is the Danger Theory?

A

molecules from mitochondria acts as DAMPs and trigger an immune response that is similar to the response to a pathogen

24
Q

How do senescent cells relate to the Danger Theory?

A
  • they release molecules that trigger immune response called DAMPs (damage-associated molecular patterns)
  • response is similar to response to dangerous pathogens
25
Q

How do mitochondria relate to the Danger Theory?

A
  • mitochondria are derived from bacteria, evidenced by their circular DNA in plasmids
  • normally this DNA is buried deep in the mito where the immune system doesn’t see it
  • but when the mito starts to lose function, they get leaky and some plasmid DNA escapes
  • this DNA looks just like bacterial DNA, so the immune system is activated against it
  • in this way, the mito DNA acts as a DAMP and causes an immune response like you would get to a pathogen
26
Q

How is mitophagy triggered?

A
  • triggered by accumulation of ubiquitinated proteins on damaged or stressed mitochondria (large proteins that flag the mito for lysosomes)
  • they are degraded by lysosomes instead of the entire cell dying
27
Q

How does mitophagy change with age?

A
  • mitophagy declines with age
  • leads to increases ROS and DAMPs
  • leads to oxidative stress and inflammation
  • that coupled with reduced bioenergetics (less good at making ATP)
  • results in age related disease
28
Q

Mitochondrial stress is not always bad becuase:

A
  • ROS are important for antioxidant production
  • exercise stimulates ROS production AND antioxidant production (which can be inhibited by oral antioxidants)
  • ROS are important for wound healing