Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology.
In yeast, C-tail-anchored mitochondrial outer membrane protein Fis1 recruits the mitochondrial-fission-regulating GTPase Dnm1 to mitochondrial fission sites. However, the function of its mammalian homologue remains enigmatic because it has been reported to be dispensable for the mitochondrial recruitment of Drp1, a mammalian homologue of Dnm1. We identified TBC1D15 as a Fis1-binding protein in HeLa cell extracts. Immunoprecipitation revealed that Fis1 efficiently interacts with TBC1D15 but not with Drp1. Bacterially expressed Fis1 and TBC1D15 formed a direct and stable complex. Exogenously expressed TBC1D15 localized mainly in cytoplasm in HeLa cells, but when coexpressed with Fis1 it localized to mitochondria. Knockdown of TBC1D15 induced highly developed mitochondrial network structures similar to the effect of Fis1 knockdown, suggesting that the TBC1D15 and Fis1 are associated with the regulation of mitochondrial morphology independently of Drp1. These data suggest that Fis1 acts as a mitochondrial receptor in the recruitment of mitochondrial morphology protein in mammalian cells.
Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
Kenta
K
Onoue
Akihiro
A
Jofuku
Reiko
R
Ban-Ishihara
Takaya
T
Ishihara
Maki
M
Maeda
Takumi
T
Koshiba
Takashi
T
Itoh
Mitsunori
M
Fukuda
Hidenori
H
Otera
Toshihiko
T
Oka
Hiroyoshi
H
Takano
Noboru
N
Mizushima
Katsuyoshi
K
Mihara
Naotada
N
Ishihara
D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034622:RNA Interference
C476525:FIS1 protein, human; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C550073:TBC1D15 protein, human