TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression

Hironori Takamura; Yoshihisa Koyama; Shinsuke Matsuzaki; Kohei Yamada; Tsuyoshi Hattori; Shingo Miyata; Kana Takemoto; Masaya Tohyama; Taiichi Katayama

doi:10.1371/journal.pone.0051912

TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression

PLoS One. 2012;7(12):e51912. doi: 10.1371/journal.pone.0051912. Epub 2012 Dec 20.

Authors

Hironori Takamura¹, Yoshihisa Koyama, Shinsuke Matsuzaki, Kohei Yamada, Tsuyoshi Hattori, Shingo Miyata, Kana Takemoto, Masaya Tohyama, Taiichi Katayama

Affiliation

¹ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan. takamura@ugscd.osaka-u.ac.jp

Abstract

Mitochondria are dynamic organelles that change in response to extracellular stimuli. These changes are essential for normal mitochondrial/cellular function and are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Although some molecules have been identified to mediate the mitochondrial fusion and fission process, the underlying mechanisms remain unclear. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecule that regulates a variety of mitochondrial functions. Here, we examined the role of TRAP1 in the regulation of morphology. Stable TRAP1 knockdown cells showed abnormal mitochondrial morphology, and we observed significant decreases in dynamin-related protein 1 (Drp1) and mitochondrial fission factor (Mff), mitochondrial fission proteins. Similar results were obtained by transient knockdown of TRAP1 in two different cell lines, SH-SY5Y neuroblastoma cells and KNS-42 glioma cells. However, TRAP1 knockdown did not affect expression levels of fusion proteins. The reduction in Drp1 and Mff protein levels was rescued following treatment with the proteasome inhibitor MG132. These results suggest that TRAP1 regulates the expression of fission proteins and controls mitochondrial fusion/fission, which affects mitochondrial/cellular function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Cell Line
Dynamins
GTP Phosphohydrolases / genetics*
GTP Phosphohydrolases / metabolism
Gene Expression
Gene Expression Regulation*
HSP90 Heat-Shock Proteins / metabolism*
Humans
Membrane Proteins / chemistry
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Mitochondria / genetics*
Mitochondria / metabolism*
Mitochondria / pathology
Mitochondrial Dynamics*
Mitochondrial Proteins / chemistry
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Molecular Sequence Data
Protein Transport

Substances

HSP90 Heat-Shock Proteins
Membrane Proteins
Mff protein, human
Microtubule-Associated Proteins
Mitochondrial Proteins
TRAP1 protein, human
GTP Phosphohydrolases
DNM1L protein, human
Dynamins

Grants and funding

This work was partially supported by the Sakamoto Research Institute of Psychopathology to HT, and by the Grant-in-Aid for Young Scientists (B) from Japan Society for the Promotion of Science to HT (No.23791332) and to SM. (No.23790224). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.