title: Light control of mitochondrial complex I activity by a photoresponsive inhibitor.
abstract: We recently developed a new class of inhibitors of bovine heart mitochondrial NADH-ubiquinone oxidoreductase (complex I), named Deltalac-acetogenin [Ichimaru et al. (2005) Biochemistry 44, 816-825]. The inhibitory potency of Deltalac-acetogenin is remarkably affected by the molecular shape of the alkyl side chains. We speculated that if the shape of the side chains can be changed by the trans-cisphotoisomerization of the azobenzene unit that is introduced into the chain moiety, the inhibitory effect could be switched on and off in a reversible manner. Such a photoresponsive inhibitor may allow rapid, remote, and noninvasive control of complex I activity. Therefore, we here synthesized Deltalac-acetogenin (3) possessing an azobenzene unit in the side chains. (1)H NMR, HPLC, and UV-visible absorption analyses indicated that the azobenzene unit in 3 is rapidly and reversibly trans-cis isomerized by photoirradiation in chloroform and ethanol. The inhibitory effect of trans,trans-3 on complex I activity in submitochondrial particles was more potent than that of cis,cis-3. When 3 was applied at the nanomolar level to complex I, the inhibitory effect was reversibly reduced and enhanced by alternating irradiation by UV and visible light, respectively. The present study gives a positive clue to the light control of complex I activity.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujita
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Murai
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nishioka
authors.forename: Hideto
authors.initials: H
authors.lastname: Miyoshi
mesh_terms: D002851:Chromatography, High Pressure Liquid; D042967:Electron Transport Complex I / Q000378:metabolism*; D007536:Isomerism; D008027:Light; D019906:Nuclear Magnetic Resonance, Biomolecular; D013056:Spectrophotometry, Ultraviolet
chemical_list: D042967:Electron Transport Complex I