What is the ER stress pathway?

What is the ER stress pathway?

ER stress occurs when the capacity of the ER to fold proteins becomes saturated. ER stress may be caused by factors that impair protein glycosylation or disulfide bond formation, or by overexpression of or mutations in proteins entering the secretory pathway.

Can apoptosis be initiated by stress?

The mitochondrial pathway is initiated by stress signals through the release of apoptogenic factors such as cytochrome c, apoptosis inducing factor (AIF), or Smac/DIABLO from the mitochondrial intermembrane space.

Does ER stress cause cell death?

ER stress-induced cell death. Under ER stress, PERK is activated and phosphorylates and inactivates eIF2a. This results in the selective induction of ATF4 and its downstream proteins CHOP and Noxa, resulting in cell death.

What are the two pathways of apoptosis?

The two main pathways of apoptosis are extrinsic and intrinsic as well as a perforin/granzyme pathway. Each requires specific triggering signals to begin an energy-dependent cascade of molecular events. Each pathway activates its own initiator caspase (8, 9, 10) which in turn will activate the executioner caspase-3.

Does ER stress cause apoptosis?

However, if ER stress is sustained and the adaptive UPR fails to eliminate unfolded/misfolded proteins, apoptosis will occur to remove the stressed cells. In recent years, a large body of studies has shown that ER stress-induced apoptosis is implicated in numerous human diseases, such as diabetes and neurogenerative diseases.

What is the relationship between stress and apoptosis in diabetes?

In recent years, a large body of studies has shown that ER stress-induced apoptosis is implicated in numerous human diseases, such as diabetes and neurogenerative diseases.

Is caspase-12 involved in ER stress-induced cell death?

Under ER stress conditions, BAX translocated to mitochondria and cytochrome c was released from mitochondria. We also demonstrated that caspase-12 was processed downstream of Apaf-1 and caspase-3, and neither overexpression nor knockdown of caspase-12 affected susceptibility of the cells to ER stress-induced cell death.

Do apaf-1-deficient MEFs activate caspase-3 under ER stress?

Despite comparable induction of ER stress in both wild type and Apaf-1-deficient cells, activation of caspase-3 was only observed in wild type, but not Apaf-1-deficient, MEFs. Under ER stress conditions, BAX translocated to mitochondria and cytochrome c was released from mitochondria.