title: Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring.
abstract: In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by neuronal activation, thereby meeting the need for local calcium buffering and maintaining the ATP supply. However, the molecular players and detailed regulatory mechanisms behind neuronal mitochondrial movement are not completely understood. Here, we found that neuronal activation-induced mitochondrial anchoring is regulated by Disrupted-in-schizophrenia 1 (DISC1), which is accomplished by functional association with Syntaphilin (SNPH). DISC1 deficiency resulted in reduced axonal mitochondrial movement, which was partially reversed by concomitant SNPH depletion. In addition, a SNPH deletion mutant lacking the sequence for interaction with DISC1 exhibited an enhanced mitochondrial anchoring effect than wild-type SNPH. Moreover, upon neuronal activation, mitochondrial movement was preserved by DISC1 overexpression, not showing immobilized response of mitochondria. Taken together, we propose that DISC1 in association with SNPH is a component of a modulatory complex that determines mitochondrial anchoring in response to neuronal activation.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Cana
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Seol-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Yeongjun
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Bo Kyoung
authors.initials: BK
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Youngsik
authors.initials: Y
authors.lastname: Woo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Choi
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Huh
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: You-Me
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea. skpark@postech.ac.kr.
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C498794:Disc1 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C573782:Miro-1 protein, mouse; D009419:Nerve Tissue Proteins; C527531:Snph protein, mouse; D020741:rho GTP-Binding Proteins
keywords: Axonal mitochondrial anchoring; DISC1; SNPH; Schizophrenia