Necroptosis is a regulated form of necrotic cell death requiring RIPK1, RIPK3, and MLKL. The final executioner step involves MLKL, which causes cell death by:

• A Oligomerising and inserting into the plasma membrane to form non-selective ion channels causing osmotic lysis ✓
• B Activating caspase-7 to cleave nuclear lamins and DNA
• C Activating gasdermin D to form pores and release IL-1beta
• D Translocating to mitochondria to release cytochrome c

Explanation

In necroptosis, RIPK3 phosphorylates MLKL (mixed lineage kinase domain-like protein), causing it to oligomerise and translocate to the plasma membrane where it forms non-selective cation channels/pores. These pores cause rapid ion influx (particularly sodium and calcium), loss of membrane integrity, osmotic swelling, and eventually membrane rupture — releasing DAMPs that drive inflammation, which is the biological significance of necroptosis compared with silent apoptosis. Gasdermin D pore formation is the executioner of pyroptosis (not necroptosis). Cytochrome c release is the intrinsic apoptosis mitochondrial step.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.