The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells.
Mitochondria are dynamic organelles that change morphology by controlled fission and fusion events. Mitochondrial fission is regulated by a conserved protein complex assembled at the outer membrane. Human MTP18 is a novel nuclear-encoded mitochondrial membrane protein, implicated in controlling mitochondrial fission. Upon overexpression of MTP18, mitochondrial morphology was altered from filamentous to punctate structures suggesting excessive mitochondrial fission. Mitochondrial fragmentation was blocked in cells coexpressing either the mitochondrial fusion protein Mfn1 or Drp1(K38A), a dominant negative version of the fission protein Drp1. Also, a loss-of function of endogenous MTP18 by RNA interference (RNAi) resulted in highly fused mitochondria. Moreover, MTP18 appears to be required for mitochondrial fission because it is blocked after overexpression of hFis1 in cells with RNAi-mediated MTP18 knockdown. In conclusion, we propose that MTP18 functions as an essential intramitochondrial component of the mitochondrial division apparatus, contributing to the maintenance of mitochondrial morphology.
Tondera
Daniel
D
Atugen AG, Robert-Rössle-Strasse 10, Otto-Warburg-Haus (80), 13125 Berlin, Germany.
Czauderna
Frank
F
Paulick
Katharina
K
Schwarzer
Rolf
R
Kaufmann
Jörg
J
Santel
Ansgar
A
D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D034281:Dynamins; D019286:Endopeptidase K; D020558:GTP Phosphohydrolases / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
C476525:FIS1 protein, human; C490021:MTFP1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D019286:Endopeptidase K; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins