Cell Stress Part 2

Question 1

What do Lysosomes normally do ?

Answer 1

Lysosomes normally supply extracellular nutrients to cells

Question 2

Lysosomes Harbour what ?

Answer 2

Lysosomes harbour many enzymes that degrade macromolecules at acidic pH

Question 3

What do Lysosomes digest ?

Answer 3

Lysosomes also digest intracellular contents acquired by autophagy This allows recycling of macromolecular building blocks during starvation Autophagy from Greek: “self-eating”

Question 4

Autophagy ?

Answer 4

Autophagy is initiated by engulfing damaged organelles and cytosol with a double membrane derived from the ER

Question 5

Functions of autophagy

Answer 5

Normal “housekeeping”  Increased to allow recycling of macromolecules under starvation conditions  Responses to viral and bacterial infections

Question 6

Cell Death

Answer 6

Necrosis

Nutrient starvation or extensive chemical damage  Cells run out of energy (ATP) 

Unable to maintain ion gradients 

Osmotic influx of water swells, bursts cells

 Cytosolic contents released; inflammation is triggered in multicellular organisms

Question 7

Cell Death

Answer 7

Apoptosis

Regulated cell death
 Removal of unwanted cells 

Surplus during development (external cues) 

Too stressed, DNA too damaged (internal state) 

Dead cells must be cleared, without inflammation

Question 8

Forms of Cell dEATH

Answer 8

Two major forms: necrosis and apoptosis 

Necrosis is passive, resulting from loss of metabolic control 

Any cell may suffer necrosis 

Inflammation results from release of cytoplasm


Apoptosis is death regulated in multicellular organisms by internal state or external cues

 Removes unwanted cells without inflammation

Question 9

Apoptosis

Answer 9

Specific external stimuli (engagement of “death receptors”), or sensing of internal state (DNA damage, mitochondrial dysfunction) 

A molecular “decision” is made, which activates caspases 

Caspases dismantle the cell without disrupting the membrane 

In whole organisms, the cell remnants can be taken up by nearby cells without inflammation or loss of tissue integrity 

Removal of “distressed” cells with minimal damage to the organism (via mitochondrial pathway) 

Or removal of cells during normal development

Question 10

Overall Summary

Answer 10

Cells can be stressed by various factors, which damage macromolecules or remove nutrients 

Most damaged cell constituents may be degraded and replaced; DNA must be repaired

 Background damage is omnipresent and inescapable 

Stress response mechanisms  are in place all the time (“constitutive”), and  are induced when cells are stressed (e.g., unfolded protein response, autophagy) or especially vulnerable (e.g., to DNA damage in mitosis) 

Acutely starved or energy-deprived cells die by necrosis (in multicellular organisms, this causes inflammation)

 In multicellular organisms, unwanted cells may die by apoptosis