ISSN:
1573-6881
Keywords:
VDAC1
;
mitochondria
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
Notes:
Abstract Point mutations at K234 and K236 in the yeast voltage-dependent anionchannel 1 (VDAC1) of the mitochondrial outer membrane have been shown tomarkedly impair the membrane insertion of this protein (Smith etal., 1995; Angeles et al., 1998). Mutants of this type wereexpressed in vivo in a strain of yeast with a disruption in theVDAC1 gene. Expression of the various VDAC1 forms was under the control of aGal1 promoter. Wild-type VDAC1 expression fully complemented the slow growthphenotype caused by the disruption. VDAC1 mutants in which K234 and K236 werereplaced by arginine, glutamate, or glutamine caused a more severe negativeeffect on growth. This effect appeared to be dominant since the mutant VDAC1forms suppressed growth in a yeast strain that retained its VDAC1 gene. Thisapparent dominant negative effect on growth did not seem to be specific forany stage of the cell cycle. However, the growth defect was not lethal as theaffected cells still could accumulate the vital stain, FUN1. Expression of amutant in which K234 had been replaced by glutamate had more serious negativegrowth effects than did a similar mutation at K236. Expression ofΔ71-116 VDAC1 complemented the VDAC1 disruption; however, expression ofthe same deletion mutant in which the lysines corresponding to K234 and K236were mutated to glutamate severely impaired growth. These results have shownthat a deficiency of lysine at positions 234 and 236 in VDAC1 causes anonlethal growth defect that is more severe than deletion of 45 amino acidsfrom VDAC1 or disruption of the VDAC1 gene. They also indicate that there is ahierarchy in the importance of these lysines with mutations at K234 being themore serious.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005403928641
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