Mutations in the voltage-dependent anion channel of the mitochondrial outer membrane cause a dominant nonlethal growth impairment

Rowena Angeles, Janet Devine, Ron Barret, Dennis Goebel, Elizabeth Blachyl-Dyson, Michael Forte, Roy McCauley

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Point mutations at K234 and K236 in the yeast voltage-dependent anion channel I (VDAC1) of the mitochondrial outer membrane have been shown to markedly impair the membrane insertion of this protein (Smith et al., 1995; Angeles et al., 1998). Mutants of this type were expressed in vivo in a swain of yeast with a disruption in the VDAC1 gene. Expression of the various VDAC1 forms was under the control of a Gall promoter. Wild-type VDAC1 expression fully complemented the slow growth phenotype caused by the disruption. VDAC1 mutants in which K234 and K236 were replaced by arginine, glutamate, or glutamine caused a more severe negative effect on growth. This effect appeared to be dominant since the mutant VDAC1 forms suppressed growth in a yeast strain that retained its VDAC1 gene. This apparent dominant negative effect on growth did not seem to be specific for any stage of the cell cycle. However, the growth defect was not lethal as the affected cells still could accumulate the vital stain, FUNI. Expression of a mutant in which K234 had been replaced by glutamate had more serious negative growth effects than did a similar mutation at K236. Expression of A71-116 VDAC1 complemented the VDAC1 disruption; however, expression of the same deletion mutant in which the lysines corresponding to K234 and K236 were mutated to glutamate severely impaired growth. These results have shown that a deficiency of lysine at positions 234 and 236 in VDAC1 causes a nonlethal growth defect that is more severe than deletion of 45 amino acids from VDAC1 or disruption of the VDAC1 gene. They also indicate that there is a hierarchy in the importance of these lysines with mutations at K234 being the more serious.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalJournal of Bioenergetics and Biomembranes
Volume31
Issue number2
DOIs
StatePublished - 1999

Fingerprint

Voltage-Dependent Anion Channels
Mitochondrial Membranes
Mutation
Growth
Lysine
Yeasts
arginine glutamate
Glutamic Acid
Genes
Glutamine
Point Mutation
Cell Cycle
Membrane Proteins
Coloring Agents
Phenotype
Amino Acids

Keywords

  • Mitochondria
  • VDAC1

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Mutations in the voltage-dependent anion channel of the mitochondrial outer membrane cause a dominant nonlethal growth impairment. / Angeles, Rowena; Devine, Janet; Barret, Ron; Goebel, Dennis; Blachyl-Dyson, Elizabeth; Forte, Michael; McCauley, Roy.

In: Journal of Bioenergetics and Biomembranes, Vol. 31, No. 2, 1999, p. 143-151.

Research output: Contribution to journalArticle

Angeles, Rowena ; Devine, Janet ; Barret, Ron ; Goebel, Dennis ; Blachyl-Dyson, Elizabeth ; Forte, Michael ; McCauley, Roy. / Mutations in the voltage-dependent anion channel of the mitochondrial outer membrane cause a dominant nonlethal growth impairment. In: Journal of Bioenergetics and Biomembranes. 1999 ; Vol. 31, No. 2. pp. 143-151.
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