Mixed lineage kinase domain-like pseudokinase: Conventional (necroptosis) and unconventional

Tuna Onal1, Melike Ozgul-Onal2, Ilana Chefetz3

  • 1Faculty of Medicine, Department of Histology and Embryology, Bandirma Onyedi Eylul University, Balikesir, Turkey; The Hormel Institute, University of Minnesota, Austin, MN, United States.

Insights

Mixed lineage kinase domain-like pseudokinase (MLKL) is crucial for programmed cell necrosis (necroptosis). Understanding MLKL

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Pathology

Background:

  • Mixed lineage kinase domain-like pseudokinase (MLKL) is the key mediator of necroptosis, a programmed cell death pathway.
  • Necroptosis is a caspase-independent cell death mechanism implicated in inflammatory diseases and cancer.
  • Targeting necroptosis offers a potential strategy against apoptosis-resistant cancers.

Purpose of the Study:

  • To review the diverse intracellular functions of MLKL.
  • To explore MLKL's roles in both necroptosis-dependent and independent cellular processes.
  • To highlight MLKL's involvement in autophagy, inflammation, tissue regeneration, and endosomal trafficking.

Main Methods:

  • Literature review of studies on MLKL function.
  • Analysis of necroptosis signaling pathways.
  • Examination of MLKL's role in various cellular processes.

Main Results:

  • MLKL is essential for necroptosis execution.
  • MLKL regulates cellular processes beyond necroptosis.
  • MLKL is implicated in autophagy, inflammation, tissue repair, and endosomal dynamics.

Conclusions:

  • MLKL possesses multifaceted roles in cellular functions.
  • Further research into MLKL's functions can lead to novel therapeutic targets.
  • Understanding MLKL is vital for developing new treatments for diseases involving necroptosis and inflammation.

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.7K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.5K
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.4K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K