Coronavirus – Disease, Medical Sciences Involved & Preventive Measures

Ferroptosis Cases in Severe Covid Patients

Note4Students

From UPSC perspective, the following things are important :

Prelims level: Ferroptosis

Mains level: NA

Why in the News?

Columbia University study on COVID-19 fatalities found ferroptosis as the main cause of lung cell death, advancing understanding of lung disease development.

What is Ferroptosis?

  • Ferroptosis is a type of regulated cell death characterized by the iron-dependent accumulation of lipid peroxides to lethal levels.

Other forms of cell death: 

  1. Apoptosis (highly regulated process that occurs in multicellular organisms to eliminate unwanted or damaged cells without causing inflammation),
  2. Necrosis (cell death characterized by rapid and uncontrolled cell lysis, often accompanied by inflammation and tissue damage).
  3. Autophagy (involves the degradation and recycling of cellular components through lysosomal machinery).

Mechanism of Ferroptosis:

The precise molecular mechanism underlying ferroptosis is still being elucidated, but it involves the deregulation of iron metabolism and lipid peroxidation. Here’s a simplified overview of how ferroptosis occurs:

  1. Iron Accumulation: Ferroptosis is characterized by the accumulation of iron within cells, particularly in the form of labile iron pools. Excess iron can lead to the generation of reactive oxygen species (ROS) through Fenton chemistry.
  2. Lipid Peroxidation: ROS generated from excess iron promotes lipid peroxidation, particularly of polyunsaturated fatty acids (PUFAs) within cell membranes. Lipid peroxides accumulate and propagate, leading to membrane damage and loss of membrane integrity.
  3. Glutathione Depletion: Glutathione (GSH) is an antioxidant that helps to neutralize ROS and prevent lipid peroxidation. In ferroptosis, there is a depletion of cellular GSH levels, which impairs the cell’s ability to counteract oxidative stress.
  4. GPX4 Inhibition: Glutathione peroxidase 4 (GPX4) is an enzyme that catalyzes the reduction of lipid hydroperoxides to their corresponding alcohols, thereby protecting cells from lipid peroxidation. In ferroptosis, GPX4 activity is inhibited, leading to the accumulation of lipid peroxides and cell death.
  5. Mitochondrial Dysfunction: Ferroptosis is associated with mitochondrial dysfunction, including alterations in mitochondrial membrane potential and morphology, as well as disruption of mitochondrial metabolism and bioenergetics.
  6. Cellular Consequences: The accumulation of lipid peroxides and mitochondrial dysfunction ultimately leads to cellular damage, loss of cell membrane integrity, and cell death by ferroptosis.

Significance of the Study

  • Targeting and preventing ferroptosis could offer novel treatment avenues for COVID-19 lung disease and its possible future mutations.
  • Inhibiting this form of cell death may help improve the treatment outcomes for severe cases of COVID-19.

PYQ:

[2020] COVID-19 pandemic has caused unprecedented devastation worldwide. However, technological advancements are being availed readily to win over the crisis. Give an account of how technology was sought to aid management of the pandemic.

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