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Apolipoprotein-L Functions in Membrane Remodeling

Etienne Pays1

  • 1Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, 6041 Gosselies, Belgium.

Cells
|January 8, 2025
PubMed

Insights

Mammalian Apolipoprotein-L proteins (APOLs) regulate membrane dynamics during infection. APOL1 and APOL3 control membrane remodeling, influencing inflammation, mitophagy, and apoptosis through interactions with key cellular components.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Mammalian Apolipoprotein-L families (APOLs) are membrane-interacting proteins.
  • Some APOLs are involved in controlling membrane dynamics, including traffic, fission, and fusion.
  • Human APOL1 and APOL3 are implicated in membrane remodeling during pathogen infection.

Purpose of the Study:

  • To elucidate the roles of APOL1 and APOL3 in membrane remodeling during infection-induced inflammation.
  • To investigate the molecular mechanisms by which APOLs regulate cellular processes like mitophagy, apoptosis, and phagolysosome formation.
  • To explore the broader functions of different APOL isoforms in inflammatory conditions.

Main Methods:

  • Investigated APOL1-NM2A interactions and their role in vesicle trafficking.
  • Analyzed APOL3 interactions with PI4KB, NCS1, CALN1, and ARF1 to understand PI(4)P synthesis.
  • Examined the impact of APOL3 on STING activation, mitophagy, apoptosis, and phagolysosome formation.
  • Studied APOL7C in antigen cross-presentation and APOLd1/mAPOL6 in angiogenesis/adipogenesis.

Main Results:

  • APOL1 directs Golgi-derived vesicles carrying ATG9A, APOL3, PI4KB, and STING to MERCSs for mitophagy and apoptosis.
  • APOL3 controls PI(4)P synthesis via interactions with PI4KB and its regulators, impacting STING activation, mitophagy, and phagolysosome formation.
  • APOL3 facilitates mitophagosome-endolysosome fusion, while APOL7C is involved in phagosome permeabilization.
  • APOLd1 and mAPOL6 promote angiogenesis and adipogenesis, respectively, under inflammatory conditions.

Conclusions:

  • APOL1 and APOL3 play critical, distinct roles in membrane remodeling associated with infection and inflammation.
  • APOL3-mediated PI(4)P synthesis is essential for regulating inflammatory signaling and cellular defense mechanisms.
  • Various APOL isoforms contribute to diverse membrane-related processes, highlighting their multifaceted roles in immunity and tissue homeostasis.
Keywords:
APOL1 nephropathyAPOL1 risk variantsAPOL3 antibacterial activityadipogenesisangiogenesisantigen cross-presentationkidney diseasemembrane fissionmembrane fusionmitophagy

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