APOOL is a cardiolipin-binding constituent of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria

PLoS One. 2013 May 21;8(5):e63683. doi: 10.1371/journal.pone.0063683. Print 2013.

Abstract

Mitochondrial cristae morphology is highly variable and altered under numerous pathological conditions. The protein complexes involved are largely unknown or only insufficiently characterized. Using complexome profiling we identified apolipoprotein O (APOO) and apolipoprotein O-like protein (APOOL) as putative components of the Mitofilin/MINOS protein complex which was recently implicated in determining cristae morphology. We show that APOOL is a mitochondrial membrane protein facing the intermembrane space. It specifically binds to cardiolipin in vitro but not to the precursor lipid phosphatidylglycerol. Overexpression of APOOL led to fragmentation of mitochondria, a reduced basal oxygen consumption rate, and altered cristae morphology. Downregulation of APOOL impaired mitochondrial respiration and caused major alterations in cristae morphology. We further show that APOOL physically interacts with several subunits of the MINOS complex, namely Mitofilin, MINOS1, and SAMM50. We conclude that APOOL is a cardiolipin-binding component of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria. Our findings further assign an intracellular role to a member of the apolipoprotein family in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins / metabolism*
  • Cardiolipins / metabolism*
  • Cattle
  • Down-Regulation
  • HeLa Cells
  • Humans
  • Mammals / metabolism*
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / ultrastructure
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / metabolism*
  • Multiprotein Complexes / metabolism*
  • Muscle Proteins / metabolism*
  • Oxygen Consumption
  • Protein Binding

Substances

  • APOOL protein, human
  • Apolipoproteins
  • Cardiolipins
  • IMMT protein, human
  • MINOS1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • Muscle Proteins

Grant support

This work was supported by the the Cluster of Excellence Frankfurt Macromolecular Complexes at the Goethe University Frankfurt DFG project EXC 115 (AR, TW, UB, IW), by the Deutsche Forschungsgemeinschaft SFB815 Project Z1 (UB, HH, IW) and The BMBF 01GM1113B- mitoNET (IW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.