Yol027/yLetM1
encodes a mitochondrial protein involved in the control of membrane potential
and organelle volume.
Karin Nowikowski,
Gabor Zsurka, Martin Kolisek, Ludmilla Zotova, Rudolf Schweyen
Microbiology and Genetics, University of Vienna, Dr. Bohrgasse 9, Vienna,
A-1030, Austria (rudolf.schweyen@univie.ac.at)
The LetM1 gene product (LetM1p), a ubiquitous membrane protein with about >35% sequence identity among eukaryotes, is shown here to be an integral component of the inner mitochondrial membrane. Deletion of LetM1 in yeast (letM1D mutant) results in mitochondrial dysfunction. Characteristic features of the mutant are increased cation contents, particularly of K+ in mitochondria and concomitantly low mitochondrial membrane potential and massive swelling of the organelle. Addition of nigericin, a H+/K+ exchanger, to isolated mitochondria restores their membrane potential. These results identify LetM1 as the first mitochondrial inner membrane protein essential for the maintenance of proper K+ homeostasis and volume of the organelle. Expression of human LetM1 in yeast complements the mutant phenotype, pointing to functional conservation of LetM1 proteins from yeast to man. Deletion of the human LetM1 gene has been implicated in causing the classical clinical manifestations of the segmental aneusomy Wolf-Hischhorn syndrome which includes, besides congenital facial malformations and growth retardation, epileptic seizures.