Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 176-185 |
| Number of pages | 10 |
| Journal | Journal of Cell Science |
| Volume | 126 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2013 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology. / Onoue, Kenta; Jofuku, Akihiro; Ban-Ishihara, Reiko; Ishihara, Takaya; Maeda, Maki; Koshiba, Takumi; Itoh, Takashi; Fukuda, Mitsunori; Otera, Hidenori; Oka, Toshihiko; Takano, Hiroyoshi; Mizushima, Noboru; Mihara, Katsuyoshi; Ishihara, Naotada.
In: Journal of Cell Science, Vol. 126, No. 1, 01.01.2013, p. 176-185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology
AU - Onoue, Kenta
AU - Jofuku, Akihiro
AU - Ban-Ishihara, Reiko
AU - Ishihara, Takaya
AU - Maeda, Maki
AU - Koshiba, Takumi
AU - Itoh, Takashi
AU - Fukuda, Mitsunori
AU - Otera, Hidenori
AU - Oka, Toshihiko
AU - Takano, Hiroyoshi
AU - Mizushima, Noboru
AU - Mihara, Katsuyoshi
AU - Ishihara, Naotada
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875581921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875581921&partnerID=8YFLogxK
U2 - 10.1242/jcs.111211
DO - 10.1242/jcs.111211
M3 - Article
C2 - 23077178
AN - SCOPUS:84875581921
VL - 126
SP - 176
EP - 185
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 1
ER -