The tumor suppressor cybL, a component of the respiratory chain, mediates apoptosis induction.
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.
Albayrak
Timur
T
Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
Scherhammer
Volker
V
Schoenfeld
Nicole
N
Braziulis
Erik
E
Mund
Thomas
T
Bauer
Manuel K A
MK
Scheffler
Immo E
IE
Grimm
Stefan
S
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*
D025521:Tumor Suppressor Proteins; C478189:respiratory complex II; D042963:Electron Transport Complex II