Trypanosome Letm1 protein is essential for mitochondrial potassium homeostasis

0420953 - BC 2015 RIV US eng J - Článek v odborném periodiku
Hashimi, Hassan - McDonald, Lindsay M. - Stříbrná, Eva - Lukeš, Julius
Trypanosome Letm1 protein is essential for mitochondrial potassium homeostasis.
Journal of Biological Chemistry. Roč. 288, č. 37 (2013), s. 26914-26925. ISSN 0021-9258. E-ISSN 1083-351X
Grant CEP: GA ČR GAP305/12/2261
Institucionální podpora: RVO:60077344
Klíčová slova: Bioenergetics * Letm1 * Mitochondria * Potassium Transport * Translation * Trypanosome
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.600, rok: 2013

Letm1 is a conserved protein in eukaryotes bearing energized mitochondria. Hemizygous deletion of its gene has been implicated in symptoms of the human disease Wolf-Hirschhorn syndrome. Studies almost exclusively performed in opisthokonts have attributed several roles to Letm1, including maintaining mitochondrial morphology, mediating either calcium or potassium/proton antiport, and facilitating mitochondrial translation. We address the ancestral function of Letm1 in the highly diverged protist and significant pathogen, Trypanosoma brucei. We demonstrate that Letm1 is involved in maintaining mitochondrial volume via potassium/proton exchange across the inner membrane. This role is essential in the vector-dwelling procyclic and mammal-infecting bloodstream stages as well as in Trypanosoma brucei evansi, a form of the latter stage lacking an organellar genome. In the pathogenic bloodstream stage, the mitochondrion consumes ATP to maintain an energized state, whereas that of T. brucei evansi also lacks a conventional proton-driven membrane potential. Thus, Letm1 performs its function in different physiological states, suggesting that ion homeostasis is among the few characterized essential pathways of the mitochondrion at this T. brucei life stage. Interestingly, Letm1 depletion in the procyclic stage can be complemented by exogenous expression of its human counterpart, highlighting the conservation of protein function between highly divergent species. Furthermore, although mitochondrial translation is affected upon Letm1 ablation, it is an indirect consequence of K(+) accumulation in the matrix.
Trvalý link: http://hdl.handle.net/11104/0227478