Intrinsic form of apoptosis: definition, process (2023)

Intracellular stimuli, such as DNA damage, trigger apoptosis through the intrinsic path.The path of intrinsic apoptosis, which consists of preserved signal proteins, is physically connected to mitochondria and is sensitive to mitochondrial oxidative stress in vertebrates.-BAX and gene BCL-2 apoptotic regulatory protein.

What is the path of intrinsic apoptosis?

• Intrinsic apoptosis path initiators include chemotherapy and/or radiotherapy.It is triggered by a variety of external and endogenous events, including DNA damage, ischemia and oxidative stress.
• The functional sequence of proapoptotic signal transmission on the intrinsic path is the interruption of the mitochondrial membrane and the release of cytochrome C in cytoplasm9.
• This complex hydrolyzed adenosine triphosphate to divide and activate caspase-9.
• It differs completely from extracellular signs, which are usually generated by cytotoxic immune cells and apoptosis mainly induce the extrinsic path.

Process and regulation of the path of intrinsic apoptosis

(Video) "What is Apoptosis?" The Apoptotic Pathways and the Caspase Cascade

• The intrinsic path of apoptosis promotes apoptosis by directly activating caspase-3 or dividing offering (BH3 agonist interaction of domestic death), which is a mitochondrial malfunction, the release of cytochrom C and the activation of caspasen-9 lead and caspases inNumerous outers improves the apoptotic properties of Caspase-3, such as DNA fragmentation and cell death.
• B cell lymphoma (BCL-2-2) family controls the activation of the intrinsic path with great accuracy.
• A protein subgroup, including IDB, Bad, Bim, BMF, Puma and Noxa, has a pro-apoptotic activity and includes a single domain of BCL-2 homology (BH3 proteins).
• The first subgroup consists of pro-apoptotic proteins, such as BCL-2 (BAX), antagonist/killer of BCL-2 (BAK) and the BCL-2 Family Apoptosis Regulator (BOK),While the second subgroup of anti-apoptotic proteins such as BCL-2, BCL-XL and MCL-1.
• BCL family members associated with mitochondrial membrane influence the path of mitochondria, including proapoptotic regulatory proteins and BCL-2 anti-apoptotic regulatory proteins.
• Proapopototic chemicals induce permeabilization of the external membrane of mitochondria, which leads to the discharge of cytochrome C, APAF-1 and Caspase-9 bind to cytosol to form the apoptosome complex.
• This activates the effective caspases, stimulating caspase-9.In addition, mitochondria releases a protein known as SMAC/Diablo in Citosol.Anti-apoptotic proteins (IAPs), inhibit.
• BCL-2 and BCL-XL anti-apoptotic proteins block the release of mitochondria cytochrome C, while pro-apoptotic proteins BAX, BAK and IDB improve its release.
• Citochrom C and deoxyadosinthrifosphate (DATP) with APAF-1 to create a multimeter complex attracts and activates pro-caspase-9 protease, an apoptosis-mediated manipulation protease that culminates in cell apoptosis.
• Caspasen-2, Caspase-8, Caspase-9 and Caspase-10 are involved at the beginning of apoptosis during this process.
• Caspasen -3, -6 and -7 play a role in apoptosis.Caspases 3 and 7 regulate the inhibition of DNA repair and start the DNA -abbau.tar beyond the caspase -6 blade and cytoskeleton.

Path of intrinsic apoptosis in pathophysiology

• The vast majority of chemotherapeutic and directed cancer treatments remove tumor cells, creating pro-death signs that trigger the intrinsic apoptotic mechanism of programmed cell death.
• The point without return on the apoptotic cascade is the permission of the Mitochondrial External Membrane (Momp);Mitochondrial permeabilization leads to the creation of an apoptosome that allows the activation of the caspase and then activates the other license plates of apopootic cell death.
• A sensitive balance between proapoptotic and anti-apoptotic family molecules BCL-2 controls the cell decision to activate Momp.
• The inability of tumor cells to suffer apoptosis due to anomalies on the intrinsic apoptotic path is one of the causes of chemotherapy resistance (eg changes in P53).Despite significant treatment, many tumors still have unsatisfactory healing rates.
• Part of the tumors is now accessible to healing therapy due to the proliferation of cytotoxic chemotherapy, although resistance to intrinsic treatment of individual patients is difficult to anticipate.
• The wave of molecularly targeted medicinal medications focused on drug mutations and therefore is limited to selected subgroups of patients.
• The intrinsic path of mitochondria of apoptosis is a prospective goal for future therapeutic agents, and its successful goal has the potential to change the therapeutic scenario for the treatment of a variety of malignancy.

Common questions

References

• https://www.creative-diagnostics.com/intrinsic-apoptosis-pathway.htm
• https://en.wikipedia.org/wiki/Apoptose
• https://www.intechopen.com/chapters/38236
• https://www.sinobiological.com/research/signal-transduction/intrinsic-apoptose
• https://www.researchgate.net/figure/The-extrinsic-and-intrinsic-apoptotic-pathways-The-extrinsic-pathway-is-initiated-by_fig1_320542263
• https://teachmephysiology.com/biochemistry/cell-growth-death/apoptose/
• https://www.creative-diagnostics.com/intrinsic-apoptosis-pathway.htm
• https://www.semanticscholar.org/paper/The-Intrinsic-Pathway-of-Apoptosis-and-%3A-An-Update-Mokbel-Mokbel/e04558f6f8b82037be2b502992c2a64cc4b43a57
• https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/intrinsic-apoptosis