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SUMMARY:Mitochondria\, ROS and yeast ageing - Michael Breitenbach\, Univer
 sity of Salzburg
DTSTART:20131111T140000Z
DTEND:20131111T150000Z
UID:TALK48742@talks.cam.ac.uk
CONTACT:35225
DESCRIPTION:In this presentation I will talk about a   yeast deletion muta
 nt in the gene AFO1\, coding for a mitochondrial ribosomal protein\, which
  confers respiratory deficiency\, resistance to several oxidants\, and a m
 arked increase of the  replicative lifespan. The mutant grows rapidly  on 
 glucose media due to secondary mutations which are selected for during gro
 wth. The mutant displays an extraordinarily low level of oxygen radicals. 
 We show that the mutant strain grows rapidly and produces ethanol and biom
 ass on glucose with a kinetics comparable to wild type\, in stark contrast
  to a bona fide ethidium bromide induced rho-zero strain\, which grows slo
 wly. The growth phenotypes were shown to be the same in three quite differ
 ent genetic backgrounds\, two of them completely prototrophic\, and seem t
 o be dependent on secondary mutations in ATP3. In an evolutionary experime
 nt starting with a diploid rho-zero strain\, the fast growing respiratory 
 deficient strains contained dominant point mutations in ATP3\, which after
  PCR cloning and introduction into rho-zero strains induced rapid growth. 
 Adenine nucleotide levels are not significantly different in the fast and 
 slow-growing strains. A hypothesis not contradicting these findings is tha
 t the slow growth of ordinary rho-zero strains depends on a lack of energi
 zing the mitochondria\, not on a general low level of ATP. The mutations i
 n ATP3 could act by increasing the ATPase activity and thereby increasing 
 the membrane potential of the mitochondria\, which could improve the effic
 iency of essential metabolic pathways that have to take place in mitochond
 ria. \nIn the second part of the talk I will present the identification an
 d partial functional analysis of YNO1\, a  gene coding for a yeast NADPH o
 xidase. The enzyme is located in the ER and is responsible for the high le
 vel of superoxide production in cox4-deletion strains in the post-diauxic 
 phase. This depends on the translocation of active Ras2 to the mitochondri
 a. In wild type cells under growth conditions on glucose\, Yno1 is express
 ed at a low level\, but is needed for the formation of actin cables. The y
 no1 deletion mutant confers hypersensitivity to wiskostatin and latrunculi
 nB\, two drugs that inhibit actin cable formation. Inhibition of the actin
  cables can be overcome by adding a low non-toxic concentration of hydroge
 n peroxide. Overexpression of YNO1 leads to apoptosis\, short chronologica
 l lifespan and increased budding index in the stationary phase. The functi
 on of Yno1 was further studied by testing phenotypes of yno1 with deletion
  mutants in the actin regulatory network.
LOCATION:Sanger Lecture Theater\, Department of Biochemistry\, Sanger Buil
 ding\, 80 Tennis Court Rd
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