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Mieap forms membrane-less organelles involved in cardiolipin metabolism

Naoki Ikari1, Katsuko Honjo1, Yoko Sagami1

  • 1Division of Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Iscience
|February 7, 2024
PubMed

Insights

Mieap protein forms biomolecular condensates that regulate cardiolipin metabolism, crucial for mitochondrial function and quality control. This discovery sheds light on cancer suppression mechanisms.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Biomolecular condensates (BCs) are essential for cellular processes.
  • Mieap/Spata18, a p53-inducible protein, is implicated in colorectal tumor suppression via mitochondrial quality control.
  • The precise regulatory role of Mieap in mitochondrial function is not fully understood.

Purpose of the Study:

  • To investigate the role of Mieap in forming biomolecular condensates.
  • To elucidate the mechanism by which Mieap influences mitochondrial cardiolipin metabolism.
  • To understand Mieap's contribution to mitochondrial quality control.

Main Methods:

  • Identification of Mieap as an intrinsically disordered region (IDR)-containing protein.
  • In vitro binding assays to assess Mieap-cardiolipin interaction.
  • Lipidomic analysis to evaluate cardiolipin metabolism.
  • Phase separation assays to determine Mieap's effect on cardiolipin and associated enzymes.
  • Mitochondrial function assays in Mieap-deficient cells.

Main Results:

  • Mieap drives the formation of BCs that specifically sequester cardiolipin, a key mitochondrial phospholipid.
  • Mieap directly binds to cardiolipin and promotes its biosynthesis and remodeling.
  • Mieap BCs recruit cardiolipin biosynthetic enzymes (TAMM41, PGS1, PTPMT1, CRLS1) and remodeling enzymes (PLA2G6, TAZ).
  • Mieap deficiency leads to altered mitochondrial cristae structure, reduced respiration, and impaired ATP production.

Conclusions:

  • Mieap forms membrane-less organelles that compartmentalize and facilitate cardiolipin metabolism.
  • These Mieap-driven condensates play a critical role in maintaining mitochondrial quality control.
  • Mieap's function in cardiolipin metabolism offers new insights into its tumor-suppressive activity.
Keywords:
MetabolomicsMolecular StructureMolecular biologyMolecular interaction

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