Kucejova B, Kucej
M, Petrezselyova S, Abelovska L, Tomaska L.
A screen for nigericin -resistant yeast
mutants revealed genes controlling mitochondrial volume and
mitochondrial cation homeostasis.
Genetics. 2005 Oct;171(2):517-26
Little is known about the
regulation of ion transport across the inner mitochondrial
membrane in Saccharomyces cerevisiae. To approach this problem,
we devised a screening procedure for facilitating the
identification of proteins involved in mitochondrial ion
homeostasis. Taking advantage of the growth inhibition of yeast
cells by electroneutral K(+)/H(+) ionophore nigericin, we
screened for genetic mutations that would render cells tolerant
to this drug when grown on a nonfermentable carbon source and
identified several candidate genes including MDM31, MDM32, NDI1,
YMR088C (VBA1), CSR2, RSA1, YLR024C, and YNL136W (EAF7). Direct
examination of intact cells by electron microscopy indicated
that mutants lacking MDM31 and/or MDM32 genes contain
dramatically enlarged, spherical mitochondria and that these
morphological abnormalities can be alleviated by nigericin.
Mitochondria isolated from the Deltamdm31 and Deltamdm32 mutants
exhibited limited swelling in an isotonic solution of potassium
acetate even in the presence of an exogenous K(+)/H(+) antiport.
In addition, growth of the mutants was inhibited on
ethanol-containing media in the presence of high concentrations
of salts (KCl, NaCl, or MgSO(4)) and their mitochondria
exhibited two- (Deltamdm31 and Deltamdm32) to threefold
(Deltamdm31Deltamdm32) elevation in magnesium content. Taken
together, these data indicate that Mdm31p and Mdm32p control
mitochondrial morphology through regulation of mitochondrial
cation homeostasis and the maintenance of proper matrix
osmolarity.
PMID: 16020778 |
