Spread the love

What is the difference between intrinsic and extrinsic apoptosis pathways?

Apoptosis, also known as programmed cell death, is a highly regulated process that plays a crucial role in various physiological and pathological conditions, including aging and longevity. There are two main pathways through which apoptosis can be initiated: the intrinsic pathway and the extrinsic pathway.

Intrinsic Apoptosis Pathway

The intrinsic apoptosis pathway, also referred to as the mitochondrial pathway, is triggered by various intracellular signals, such as DNA damage, oxidative stress, or cellular stress. This pathway is regulated by members of the Bcl-2 family of proteins, which can either promote or inhibit apoptosis.

When an intracellular signal activates the intrinsic pathway, it leads to the permeabilization of the mitochondrial outer membrane. This allows the release of pro-apoptotic proteins, such as cytochrome c, from the mitochondria into the cytosol. Cytochrome c then forms a complex with Apaf-1 (apoptotic protease activating factor 1) and procaspase-9, forming the apoptosome. The apoptosome activates caspase-9, which in turn activates downstream effector caspases, leading to cell death.

See also What is ubiquitination and how does it regulate protein degradation in aging?

Extrinsic Apoptosis Pathway

The extrinsic apoptosis pathway, also known as the death receptor pathway, is initiated by the binding of extracellular death ligands, such as tumor necrosis factor (TNF) or Fas ligand (FasL), to their respective death receptors on the cell surface. This binding triggers the assembly of a death-inducing signaling complex (DISC), which recruits and activates procaspase-8.

Activated caspase-8 then directly activates downstream effector caspases, leading to apoptosis. In some cases, the extrinsic pathway can also activate the intrinsic pathway through the cleavage of Bid, a pro-apoptotic Bcl-2 family member, which promotes mitochondrial outer membrane permeabilization.

See also What role do telomeres play in aging?

Differences between Intrinsic and Extrinsic Apoptosis Pathways

While both pathways ultimately lead to apoptosis, there are several key differences between the intrinsic and extrinsic pathways:

• Initiation: The intrinsic pathway is initiated by intracellular signals, while the extrinsic pathway is initiated by extracellular death ligands binding to death receptors.
• Regulation: The intrinsic pathway is regulated by Bcl-2 family proteins, whereas the extrinsic pathway is regulated by death receptors and their ligands.
• Activation of caspases: In the intrinsic pathway, caspase-9 is activated, while in the extrinsic pathway, caspase-8 is activated.
• Induction of mitochondrial outer membrane permeabilization: Only the intrinsic pathway directly induces mitochondrial outer membrane permeabilization, leading to the release of cytochrome c.

Understanding the differences between the intrinsic and extrinsic apoptosis pathways is important for unraveling the complex mechanisms underlying cell death and its implications in various biological processes, including longevity.

See also What are the challenges in providing healthcare services to rural aging populations?

Keywords: pathway, intrinsic, apoptosis, extrinsic, pathways, mitochondrial, activates, between, regulated