title: The tumor suppressor cybL, a component of the respiratory chain, mediates apoptosis induction.
abstract: A genetic screen was established to clone apoptosis-inducing genes in a high-throughput format. It led to the isolation of several proapoptotic genes whose proteins are localized to mitochondria. One of the isolated genes is cytochrome bL (cybL also known as SDHC, CII-3, or QPs-1), a component of the respiratory chain complex II. It was further investigated because both cybL and another component of complex II, cybS, have recently been identified as tumor suppressor proteins, some of which act by controlling apoptosis. Our studies reveal that cell death induction by cybL expression is concomitant with a transient inhibition of complex II and the generation of reactive oxygen species. Importantly, cells that are constitutively deficient in cybL are resistant to a variety of proapoptotic cytostatic drugs and to the effects of the Fas receptor. Our results therefore identify complex II as a sensor for apoptosis induction and could explain the unexpected observation that complex II is inactivated in tumors.
authors.affiliation: Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
authors.forename: Timur
authors.initials: T
authors.lastname: Albayrak
authors.forename: Volker
authors.initials: V
authors.lastname: Scherhammer
authors.forename: Nicole
authors.initials: N
authors.lastname: Schoenfeld
authors.forename: Erik
authors.initials: E
authors.lastname: Braziulis
authors.forename: Thomas
authors.initials: T
authors.lastname: Mund
authors.forename: Manuel K A
authors.initials: MK
authors.lastname: Bauer
authors.forename: Immo E
authors.initials: IE
authors.lastname: Scheffler
authors.forename: Stefan
authors.initials: S
authors.lastname: Grimm
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D042963:Electron Transport Complex II / Q000378:metabolism / Q000502:physiology*; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D010084:Oxidation-Reduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D025521:Tumor Suppressor Proteins; C478189:respiratory complex II; D042963:Electron Transport Complex II