Intrinsic Route of Apoptosis: Definition, Process (2023)

Intracellular stimuli, such as DNA damage, predominantly trigger apoptosis through intrinsic pathway.Intrinsic apoptosis, which consists of preserved signaling proteins, is physically connected to the mitochondria and sensitive to mitochondrial stress in vertebrate stress.The process, including Pro or antiapopototic regulatory proteins and the BCL-2 gene.

What is the intrinsic apoptosis route?

• Intrinsic apoptosis initiators include chemotherapy and/or radiotherapy.It is triggered by a variety of external and endogenous events, including DNA damage, ischemia and oxidative stress.In addition, it is essential for the development and elimination of damaged cells.
• The functional consequence of the proopopptotic signaling in the intrinsic pathway is the interruption of the mitochondrial membrane and the release of cytochrome C in the cytoplasm, where it forms a complex or apoptosome with apoptotic protease in the activation factor 1 (APAF1) and the inactive formof the case.Phase-9.
• This complex hydrolyzes adenosine triphosphate to click Caspasa-9 and activate it.The Caspasa-9 initiator cleans and activates the caspases-3/6/7 of the albacea, resulting in cell apoptosis.
• It is completely different from extracellular signs, which are generally generated by cytotoxic immunological cells and induce apoptosis mainly through the extrinsic pathway.

Process and regulation of the intrinsic apoptosis path

• The intrinsic form of apoptosis promotes apoptosis, directly activating the Caspasa-3 or by erasing the supply (agonist of the domain interaction that interacts BH3), which results in a mitochondrial malfunction, the release of the cytochrome C and the caps ofActivation and caspases-3.In numerous organs, Caspasa-3 increases apoptotic characteristics such as DNA fragmentation and cell death.
• B cell lymphoma (BCL-2-2) The family controls the activation of the intrinsic pathway with great precision.It was initially discovered as one of the genes involved in cell death, activating propapoptotic antiapotosis or suppressing follicular lymphoma.
• A protein subgroup, which includes IDB, BAD, BIM, BMF, Puma and Noxa, has propapptotic activity and includes a unique homology domain BCL-2 (BH3 only proteins).Other protein categories include numerous BH domains.
• The first subset consists of propapptototic proteins, such as BCL-2 (Bax), BCL-2 antagonist (BAK)/BAX (BAX) and the BOK family apoptosis regulator (BOK), while BOK), while Bok), while Bok)The second subset consists of anti-anti apoptotic proteins.such as BCL-2, BCL-XL and MCL-1.
• BCL family members linked to the mitochondrial membrane affect the mitochondrial pathway, including proopaptotic regulatory proteins and BCL-2 antiapopptotic regulatory proteins.
• Proopopototic chemicals induce the permeabilization of the external mitochondrial membrane, resulting in the efflux of cytochrome C, which connects APAF-1 and Caspasa-9 in cytosol to form the apoptosome complex.
• This activates the effective caspases, stimulating Caspasa-9.In addition, mitochondria release a protein known as SMAC/devil in cytosol.Anti-apopototic (IAPS).
• BCL-2 and BCL-XL antiapopptot proteins block the liberation of cytochrome C of mitochondria, while BAX, BAK and IDB propapoptotic proteins have improved their release.
• Cytochrome C and the Desoxyadenosine Tryiff (DATP) with APAF-1 to create a multimeric complex that attracts and activates PRO-CASPASE-9 protease, an executive protease through apoptosis, culminating cell apoptosis.
• Caspasas-2, Caspasa-8, Caspasa-9 and Caspasa-10 are involved at the beginning of apoptosis throughout this process.
• Caspasas -3, -6 and -7 play a role in apoptosis.Caspasas 3 and 7 regulate the inhibition of DNA repair and initiate DNA degradation.In addition, Caspasa -6 governs the breakage of the blade and the cytoskeleton.

Intrinsic apoptosis in pathophysiology

• The vast majority of chemotherapeutic and directed cancer treatments eradicate tumor cells, generating pro-death signs that trigger the intrinsic apopptotic mechanism of programmed cell death.
• The point of no return in the apoptotic waterfall is the permeabilization of the mitochondrial external membrane (MOMP);Mitochondrial permeabilization leads to the creation of an apoptosome, which allows the activation of the caspase and subsequently activates the other characteristics of the death of apoptotic cells.
• A delicate balance between propoopptotic and antiapopptotic family molecules BCL-2 controls the cell decision to activate MOMP.
• The inability of tumor cells to suffer apoptosis due to intrinsic abnormalities of apaptotic hair is one of the causes of chemotherapy resistance (for example, changes in P53).Many tumors continue to have unsatisfactory healing rates, despite the main advances in treatment.
• A fraction of tumors is now subject to healing therapy as a result of the proliferation of cytotoxic chemotherapy, despite the fact that the intrinsic resistance of the treatment of individual patients is difficult to anticipate.
• The molecularly directed drug wave has concentrated on drug personnel mutations and, consequently, is limited to the selection of patient subsets.
• The intrinsic mitochondrial route of apoptosis is a prospective objective for future therapy, and its successful direction has the potential to transform the therapeutic landscape to treat a variety of malignancy.

Frequent questions

References

• https://www.creative-diagnostics.com/intrinsic-apoptosis-pathway.htm
• https://en.wikipedia.org/wiki/Apoptosis
• https://www.intechopen.com/chapters/38236
• https://www.sinobiological.com/research/signal-transduction/intrinsic-apoptosis
• 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/apoptosis/
• 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