title: TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression.
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.
authors.affiliation: 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
authors.forename: Hironori
authors.initials: H
authors.lastname: Takamura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.forename: Kana
authors.initials: K
authors.lastname: Takemoto
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D021381:Protein Transport
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008565:Membrane Proteins; C533267:Mff protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C092306:TRAP1 protein, human; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins