Publications

• Mitoguardin regulates mitochondrial fusion through MitoPLD and is required for neuronal homeostasis.

  Zhang Y., Liu X., Bai J., Tian X., Zhao X., Liu W., Duan X., Shang W., Fan H.Y., Tong C.

  Mitochondria undergo frequent morphological changes through fission and fusion. Mutations in core members of the mitochondrial fission/fusion machinery are responsible for severe neurodegenerative diseases. However, the mitochondrial fission/fusion mechanisms are poorly understood. We found that t ... >> More

  Mitochondria undergo frequent morphological changes through fission and fusion. Mutations in core members of the mitochondrial fission/fusion machinery are responsible for severe neurodegenerative diseases. However, the mitochondrial fission/fusion mechanisms are poorly understood. We found that the loss of a mitochondrial protein encoding gene, mitoguardin (miga), leads to mitochondrial defects and neurodegeneration in fly eyes. Mammals express two orthologs of miga: Miga1 and Miga2. Both MIGA1 and MIGA2 form homotypic and heterotypic complexes on the outer membrane of the mitochondria. Loss of MIGA results in fragmented mitochondria, whereas overexpression of MIGA leads to clustering and fusion of mitochondria in both fly and mammalian cells. MIGA proteins function downstream of mitofusin and interact with MitoPLD to stabilize MitoPLD and facilitate MitoPLD dimer formation. Therefore, we propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. << Less

  Mol. Cell 61:111-124(2016) [PubMed] [EuropePMC]

• A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis.

  Choi S.Y., Huang P., Jenkins G.M., Chan D.C., Schiller J., Frohman M.A.

  Fusion of vesicles into target membranes during many types of regulated exocytosis requires both SNARE-complex proteins and fusogenic lipids, such as phosphatidic acid. Mitochondrial fusion is less well understood but distinct, as it is mediated instead by the protein Mitofusin (Mfn). Here, we ide ... >> More

  Fusion of vesicles into target membranes during many types of regulated exocytosis requires both SNARE-complex proteins and fusogenic lipids, such as phosphatidic acid. Mitochondrial fusion is less well understood but distinct, as it is mediated instead by the protein Mitofusin (Mfn). Here, we identify an ancestral member of the phospholipase D (PLD) superfamily of lipid-modifying enzymes that is required for mitochondrial fusion. Mitochondrial PLD (MitoPLD) targets to the external face of mitochondria and promotes trans-mitochondrial membrane adherence in a Mfn-dependent manner by hydrolysing cardiolipin to generate phosphatidic acid. These findings reveal that although mitochondrial fusion and regulated exocytic fusion are mediated by distinct sets of protein machinery, the underlying processes are unexpectedly linked by the generation of a common fusogenic lipid. Moreover, our findings suggest a novel basis for the mitochondrial fragmentation observed during apoptosis. << Less

  Nat. Cell Biol. 8:1255-1262(2006) [PubMed] [EuropePMC]

• The bond hydrolyzed by cardiolipin-specific phospholipase D.

  Astrachan L.

  Biochim Biophys Acta 296:79-88(1973) [PubMed] [EuropePMC]

• Cardiolipin: a stereospecifically spin-labeled analogue and its specific enzymic hydrolysis.

  Cable M.B., Jacobus J., Powell G.L.

  The spin-labeled cardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-(16-doxylstearoyl)glycero(3)phosphol]-sn-glycerol has been prepared. The stereoselective synthesis makes use of the monolysocardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-lyso-sn-glycero(3)phospho]-sn-glycerol, available from the stereo ... >> More

  The spin-labeled cardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-(16-doxylstearoyl)glycero(3)phosphol]-sn-glycerol has been prepared. The stereoselective synthesis makes use of the monolysocardiolipin 1-(3-sn-phosphatidyl)-3-[1-acyl-2-lyso-sn-glycero(3)phospho]-sn-glycerol, available from the stereospecific hydrolysis of cardiolipin by phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) of Trimeresurus flavoviridis. The results of treatment of the spin-labeled cardiolipin with the cardiolipin-specific phospholipase D (phosphatidylcholine phosphatidohydrolase, EC 3.1.4.4) (Hemophilus parainfluenzae) of known specificity and with phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) of Bacillus cereus are consistent with the assigned structure. The spin-labeled cardiolipin is further characterized and the unique features of this diastereomer are discussed in the context of the unusual stereochemistry of the natural phospholipid. << Less

  Proc Natl Acad Sci U S A 75:1227-1231(1978) [PubMed] [EuropePMC]