Question

Though crucial for cell survival, mitochondria can also contribute to aging in a variety of diseases. Which of the following can be a consequence of damaged mitochondria? (Choose all that apply):

a. DNA damage

b. Accumulation of ROS in the cytosol

c. Cellular senescence

d. Apoptosis

e. Decreased mitochondrial membrane potential

Which is the following is a consequence/result of an accumulation reactive oxygen species (ROS)? Choose all that apply

a. Hypoxia

b. DNA damage

c. ER stress

d. Stabilization of Nrf2

e. Lipid peroxidation

f. Necrosis

g. Insulin resistance

h. Membrane Damage

Answer 1

Answer-1: All options are correct.

Explaination- Mitochondria is a source of mt-DNA. So, when it is damaged, it leads to damaging of mt-DNA too. Though, mt-DNA does not code for all the necessary proteins for the mitrochondrial functinaing, but it codes for some of the necessary proteins, Damaged mitochondria leads to hypoxia and this in turn causes accumulation of increased synthesis of ROS. Since, mitochondria serve as a power house of a cell, so, when it gets damaged it reduces or disrupts various important functions of cells and thus, makes it senescent. When the mitochondria gets damaged, it releases cyt-c and phosphatidylserine also gets expressed on the mitochondrial membrane which ultimately initiates apoptosis. During the damage, it compromises the homeostasis of calcium ions, as a result, they gets leaked out in the surrounding, so, membrane potential decreases and becomes negative.

Answer-2: All options are correct.

Explaination- Whenever there is a damage caused to mitochondria, it causes the accumulation of ROS and this inturn results in hypoxia condition, or vice-versa.

ROS causes DNA to damage by modifying the bases, it can break it's strand or it can also crosslink the DNA structure.

ROS can be produced inside ER and on being accumulated inside ER, it causes alteration in the natural ER homeostasis which induces ER stress.

NRF-2 is STABILIZED by the accumulated ROS. NRF-2 inturn gets activated when it senses the increased concentration of ROS within the cell and helps the cell in protection against ROS, or against proliferation of cancers caused by it.

Lipid peroxidation occurs when free radicals or ROS abstracts electrons from the cellular lipids from the cell membrane and hence, causes its damage.

Whenever, there is accumulation of ROS, it generates xathine and xanthine oxidase, that plays crucial role in apoptosis and necrosis. Necrosis occur when the concentration of xanthine oxidase. Necrosis does not cause DNA damage as it does not activates caspases.

ROS causes insulin resistance as it acts as a transcription factor in insulin receptor signalling pathway and alters the activity of GLUT-4 transporter.

ROS leads to membrane damage because it causes peroxidation of lipids present in lipid bilayer of plasma membrane.